Rozprawy doktorskie na temat „Neuropeptide Y”
Kliknij ten link, aby zobaczyć inne rodzaje publikacji na ten temat: Neuropeptide Y.
Utwórz poprawne odniesienie w stylach APA, MLA, Chicago, Harvard i wielu innych
Sprawdź 50 najlepszych rozpraw doktorskich naukowych na temat „Neuropeptide Y”.
Przycisk „Dodaj do bibliografii” jest dostępny obok każdej pracy w bibliografii. Użyj go – a my automatycznie utworzymy odniesienie bibliograficzne do wybranej pracy w stylu cytowania, którego potrzebujesz: APA, MLA, Harvard, Chicago, Vancouver itp.
Możesz również pobrać pełny tekst publikacji naukowej w formacie „.pdf” i przeczytać adnotację do pracy online, jeśli odpowiednie parametry są dostępne w metadanych.
Przeglądaj rozprawy doktorskie z różnych dziedzin i twórz odpowiednie bibliografie.
1
Diez, Margarita. "Neuropeptide expression in mouse disease models /". Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-514-x/.
Pełny tekst źródła
2
Sjödin, Paula. "Pharmacological studies of four neuropeptide Y-family receptor subtypes /". Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-5925.
Pełny tekst źródła
3
Pheng, Leng-Hong. "Caractérisation pharmacologique des récepteurs natifs du neuropeptide Y et de la nociceptine". Sherbrooke : Université de Sherbrooke, 2001.
Znajdź pełny tekst źródła
4
Brumovsky, Pablo R. "Neuropeptides, sensory neurons and pain modulation /". Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-442-2/.
Pełny tekst źródła
5
Miskelly, I. R. "Comparative analysis of parasitic nematode neuropeptide and neuropeptide receptor encoding genes". Thesis, Queen's University Belfast, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.432533.
Pełny tekst źródła
6
Guery, Sébastien. "Conception et synthèse de dérivés de l'arginine : Concepts et validation sur des récepteurs de neuropeptides". Université Louis Pasteur (Strasbourg) (1971-2008), 2003. https://publication-theses.unistra.fr/public/theses_doctorat/2003/GUERY_Sebastien_2003.pdf.
Pełny tekst źródłaStreszczenie:
La découverte de neuropeptides comme molécules pharmacologiquement actives est d'une importance considérable pour notre compréhension de la neurobiologie. Les neuropeptides peuvent agir en tant que neurotransmetteurs, neuromodulateurs et en tant qu'hormones. Ils contrôlent ou influencent de nombreux types de comportements biologiques (par exemple le comportement sexuel, le comportement alimentaire, la mémoire, l'apprentissage, la perception de la douleur, ). Certains de ces peptides appartiennent à la famille des peptides de type RF-amide qui possèdent dans leur partie C-terminale un résidu Arginine. Dans le cadre de cette thèse, nous nous sommes intéressés à deux peptides : le NPY (neuropeptide Y) et le NPFF (neuropeptide FF) qui possèdent dans leur extrémité C-terminale ce motif RF-amide. Dans un premier temps, notre travail s'est basé sur l'étude des relations structure-activité d'un ligand qui se fixe sur les récepteurs Y1 du NPY et sur les récepteurs du NPFF : le BIBP 3226. Pour ce faire, nous avons dû mettre au point une méthode de synthèse hautement convergente en solution et sur phase solide nous permettant d'obtenir avec de très bons rendements et une excellente pureté des analogues et des dérivés d'arginine. Les études de liaison spécifiques ont permis d'identifier deux composés tête de série : LPI 211 (Ki = 0,10 æM sur NPFF1 et Ki = 0,16 æM sur NPFF2) et LPI 214 (comme antagoniste des récepteurs Y1 du NPY). D'autre part, nous avons également mis au point une méthode de synthèse de composés fluorescents dérivés de l'arginine. Ces composés ont été évalués pour leur capacité à produire du FRET (5 %) sur les récepteurs Y1 du NPY et ce en vue de mettre au point une nouvelle méthode de criblage à haut débit n'utilisant pas de composés radioactifs. Enfin, nous nous sommes également intéressés à la synthèse de composés hétérocycliques peptidomimétiques de type dihydrotriazinones par l'utilisation de la réaction de Ugi. Cette voie de synthèse nous permet d'obtenir des dérivés substitués sur l'azote N1 ou sur l'azote N4 en un nombre d'étapes limitéThe discovery of neuropeptides as pharmacological active compounds is a breakthrough for our understanding in neurobiology. Neuropeptides can act as neurotransmetter, neuromodulators, and hormones. They control or influence a wide variety of biological behaviors (sexual, food intake, memory, learning, pain perception, ). Some of these peptides own to the family of RF-amide peptides which posses in their C-terminal part an arginine residue. In this work, we focused our interest on two peptides : neuropeptide FF (NPFF) and neuropeptide Y (NPY). Both of them have in their C-terminal part a RF-amide moiety. On one hand, our work was based on the study of structure activity relationship of a non specific ligand (BIBP 3226), which binds to both the NPY Y1 receptor and NPFF receptors. For this purpose, we had to optimize highly convergent synthetic methods both in solution and in solid phase in order to synthesize with high yields and purity arginine analogues and derivatives. Binding experiments highlighted two interesting hits : LPI 211 (Ki = 0,10 æM on NPFF1 and Ki = 0,16 æM on NPFF2) and LPI 214 (as antagonist of NPY on Y1 receptor). On the other hand, we have also performed an efficient method for the preparation of fluorescent arginine derivatives. These compounds were tested for their ability to produce FRET (5 %) on Y1 receptors in order to create a new high throughput screening method. Finally, we developed an original preparation of heterocyclic peptidomimetic compounds like dihydrotriazones by the use of Ugi four component reactions. This way of synthesis allowed us to obtain N1 substituted or N4 substituted dihydrotriazinones with a limited number of steps
7
Bjellerup, Per. "Biochemical characterisation and clinical correlation of neuropeptides in neuroblastoma with emphasis on neuropeptide Y /". Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-4524-1/.
Pełny tekst źródła
8
Dubin, Thierry. "Le neuropeptide Y dans le phéochromocytome : étude à partir d'une série de 15 cas". Bordeaux 2, 1990. http://www.theses.fr/1990BOR23098.
Pełny tekst źródła
9
McVeigh, P. "Neuropeptide signalling in nematodes". Thesis, Queen's University Belfast, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.411747.
Pełny tekst źródła
10
Morgan, David Alexander. "The role of neuropeptides Y and neuropeptide Y receptors in the control of carbohydrate metabolism". Thesis, Imperial College London, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.267076.
Pełny tekst źródła
11
Quiroga, Artigas Gonzalo. "Light-induced oocyte maturation in the hydrozoan clytia hemisphaerica". Thesis, Paris 6, 2017. http://www.theses.fr/2017PA066284/document.
Pełny tekst źródłaStreszczenie:
Un contrôle précis de la maturation ovocytaire et de la ponte sont essentiels au succès de la reproduction sexuée au sein le règne animal. Ces processus sont coordonnés précisément par des signaux endocriniens et/ou environnementaux, selon les espèces, mais beaucoup reste à apprendre sur leurs régulations. Chez les cnidaires, de nombreuses méduses du groupe des hydrozoaires sont connues pour produire des gamètes en réponse à la transition nuit/jour. Pour caractériser les machineries cellulaires et moléculaires liant la réception de la lumière à l'initiation de la maturation ovocytaire, j'ai étudié la méduse hydrozoaire Clytia hemisphaerica. Mon travail de thèse s’est découpé en trois parties, chacune impliquant l'identification d'un composant moléculaire clé de ce processus.Mon étude initiale faisait partie d'une collaboration avec N. Takeda (Asamushi) et R. Deguchi (Sendai), chercheurs qui avaient, avant le début de ma thèse, identifié chez Clytia les Hormones d'Incitation de Maturation ovocytaire endogènes (MIH) comme étant des tétrapeptides de type WPRPamide, produit par clivage de deux précurseurs à neuropeptides. J'ai montré par hybridation in situ et immunofluorescence que les deux gènes précurseurs du MIH sont exprimés par un type de cellules neurosécrétrices localisées au niveau de l’ectoderme de la gonade, et que les peptides MIH sont sécrétés par ces mêmes cellules suite à une stimulation lumineuse. Cette étude a posé les bases permettant l'identification des régulateurs agissant en amont et en aval du MIH, et plus spécifiquement ceux impliqués dans la photoréception de l’ectoderme de la gonade et la réception du MIH par les ovocytes.Pour identifier le récepteur du MIH de Clytia (CheMIHR) dans les ovocytes, j'ai compilé à partir de données transcriptomiques issues de tissus de gonades, une liste de 16 protéines candidates de la famille des Récepteurs Couplés aux Protéines G (GPCR). J'ai cloné les 16 cDNAs et, utilisant une méthode de « deorphelinisation » de GPCR basée sur de la culture cellulaire (collaboration avec P. Bauknecht et G. Jékély; MPI, Tübingen), j’ai pu identifier un GPCR activée par des peptides MIH synthétiques. Sa fonction in vivo comme récepteur essentiel du MIH a été confirmée par la méthode d'édition génétique CRISPR/CAS9. La délétion ainsi produite, entraînant un déplacement du cadre de lecture au sein du gène CheMIHR, a détérioré la croissance des colonies de polypes et le comportement de ponte des méduses matures. Confirmant la fonction de CheMIHR, la maturation ovocytaire chez des mutants CheMIHR ne pouvait pas être déclenchée par la lumière ou par addition de MIH synthétiques, mais pouvait être rétablie en utilisant des analogues au cAMP, molécule connue pour agir en aval de la réception du MIH dans les ovocytes d’hydrozoaires. Des analyses phylogénétiques ont montré que Clytia MIHR est affilié à un sous-ensemble de familles de neuropeptides de bilaterians impliqués dans divers processus physiologiques, notamment la régulation de la reproduction. Des hybridations in situ sur les méduses Clytia, ont en outre montré l'expression des précurseurs de CheMIH et de CheMIHR dans des cellules neurales hors de la gonade, suggérant un rôle plus large du couple CheMIH-MIHR que la seule initiation de la maturation ovocytaire.Pour mieux comprendre la photoréception des gonades chez Clyita, j'ai montré que la ponte est sélectivement incitée par la lumière bleu-cyan, et mis en évidence, grâce à l’analyse de données de transcriptome de gonade, qu’un photopigment de la famille des Opsin (Opsin9) est hautement exprimé dans l'ectoderme. De façon saisissante, les hybridations in situ ont montré que le gène Opsin9 est exprimé dans les mêmes cellules sécrétant le MIH. L'introduction d'une mutation de changement de cadre de lecture dans le gène Opsin9 via la technologie CRISPR/Cas9 a empêché la maturation ovocytaire et la ponte des méduses mutantes en réponse à la lumièreTight control of oocyte maturation and of gamete release is essential for successful sexual reproduction in the animal kingdom. These processes are precisely coordinated by endocrine and/or environmental cues, depending on the species, but much remains to be learned about their regulation. Within the Cnidaria, many hydrozoan jellyfish are known to spawn mature gametes following dark/light transitions. To characterise the cellular and molecular machinery linking light reception and oocyte maturation initiation, I have studied the hydrozoan jellyfish Clytia hemisphaerica. My thesis work had three parts, each involving the identification of a key molecular component of this process.My initial study was part of a collaboration with N. Takeda (Asamushi) and R. Deguchi (Sendai), who identified the endogenous oocyte Maturation-Inducing Hormones (MIH) in Clytia as WPRPamide-related tetrapeptides, generated by cleavage of two neuropeptide precursors. I showed by in situ hybridization and immunofluorescence that Clytia MIH is produced by neurosecretory cells of the gonad ectoderm that co-express the two precursor genes, and that it is secreted upon light stimulation. This study paved the way for identification of regulators acting upstream and downstream of MIH release in the gonads, specifically the ones involved in photoreception in the gonad ectoderm, and in MIH reception by the oocytes. To identify the Clytia MIH receptor (CheMIHR) in the oocytes, I compiled a shortlist of 16 candidate G protein-coupled receptors (GPCRs) from gonad transcriptome data. I cloned all 16 cDNAs and, using a cell culture-based "GPCR deorphanization" assay (collaboration with P. Bauknecht and G. Jékély; MPI, Tübingen), identified one GPCR that was activated by synthetic MIH peptides. Its in vivo function as the essential MIH receptor was confirmed by CRISPR/Cas9 gene editing. Introduction of a frame-shift mutation in the CheMIHR gene impaired growth of Clytia polyp colonies and also the spawning behaviour of mature medusae. Confirming the function of CheMIHR, oocyte maturation in CheMIHR mutants could not be triggered by light or by synthetic MIH, but could be restored using cell-permeable analogues of cAMP, known to act downstream of MIH reception in hydrozoan oocytes. Phylogenetic analyses showed that Clytia MIHR is related to a subset of bilaterian neuropeptide hormone receptor families involved in diverse physiological processes, including regulation of reproduction. Accordingly, in situ hybridization showed the expression of Clytia MIH precursors and MIHR in non-gonadal neural cells, suggesting a wider role of Clytia MIH-MIHR besides oocyte maturation initiation.To address gonad photoreception, I showed that Clytia spawning is selectively induced by blue-cyan light, and then identified using gonad transcriptome data an opsin photopigment (Opsin9) highly expressed in the ectoderm. Strikingly, in situ hybridization showed that Opsin9 is expressed in the MIH-secreting cells. Introduction of a frame-shift mutation into the Opsin9 gene via CRISPR/Cas9 prevented oocyte maturation and spawning of mutant jellyfish in response to light. Anti-MIH immunofluorescence and rescue experiments with synthetic MIH showed that the essential function of Opsin9 is upstream of MIH release. Spawning in Clytia thus appears to be regulated by a dual function photosensory-neurosecretory cell type, perhaps retained from a distant metazoan ancestor
12
Ammar, Ahmed A. "Intake inhibition by neuropeptide Y /". Stockholm : Karolinska institutet, 2005. http://diss.kib.ki.se/2005/91-7140-308-6/.
Pełny tekst źródła
13
Howell, Owain W. "Neuropeptide Y modulates hippocampal neurogenesis". Thesis, University of Southampton, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.403849.
Pełny tekst źródła
14
Abusara, Osama. "Neuropeptide antagonists for cancer treatment". Thesis, University of Manchester, 2017. https://www.research.manchester.ac.uk/portal/en/theses/neuropeptide-antagonists-for-cancer-treatment(e2f22b9f-f0a7-432d-89c4-7e65a2c71b69).html.
Pełny tekst źródłaStreszczenie:
Small Cell Lung Cancer (SCLC) is an aggressive form of cancer accounting for 25% of lung cancer deaths worldwide. Treatment relies on combination chemotherapy (etoposide and cisplatin or carboplatin) with or without radiation therapy. However, disease relapse and resistance occurs quickly, prompting unmet need for alternative treatment options. One such option is the use of broad-spectrum antagonists, known as Substance P (SP) analogues. Historically, these analogues have not succeeded clinically due to low potency and bioavailability. In this project, novel SP analogues were developed to address these shortfalls. A chemical strategy was designed to synthesise novel short peptides including DMePhe-DTrp-Phe-DTrp-Leu-NH2 (25) as the new lead. Fmoc and Boc D-Trp derivatives with indole nitrogen having substituents (methyl, ethyl, propyl, butyl, pentyl, propargyl, benzyl and tert-prenyl) were made and characterised by 1H and 13C NMR spectroscopy and mass spectrometry (MS). These building blocks were incorporated into the first series of peptides, substituting the D-Trp residue located near the C-terminal of 25, via solid and/or liquid phase procedures. Final products were purified by RP-HPLC to >90% purity and structures verified by MS and/or 1H NMR. Cell viability assays were conducted to evaluate cytotoxicity against two SCLC cell lines: H69 (chemo-naive) and DMS79 (from a patient after treatment). The IC50 values for the D-Trp residue modified peptides were < 5 μM. One of the earliest candidates to emerge from this work was DMePhe-DTrp-Phe-DTrp(N-tert-prenyl)-Leu-NH2 (33). Subsequently, the most potent peptide was the one bearing D-Trp(N-butyl) (29) with IC50 values of 1.0 μM (H69) and 1.4 μM (DMS79), compared to the lead 25 with IC50 values of 30.7 μM (H69) and 23.0 μM (DMS79). A second series of peptides were produced to optimise 29 by incorporating a D-Trp(N-butyl) residue. The study focused on peptides by (a) modifying the N-terminal D-Trp residue, (b) modifying both D-Trp residues, (c) changing the C-terminal amide to free carboxylic acid, and (d) adding a charged amino acid (arginine) or removing a hydrophobic amino acid (leucine) to additionally aid in solubility. The most potent candidate was found to bear dual D-Trp(N-butyl) residues (35) with IC50 value of 0.6 μM (H69) and 2.3 μM (DMS79). Peptides 29 and 35 were at least 26 times more potent than SP antagonist G (SPG, previously subjected to a Phase I clinical trial), as revealed by in vitro screening in this project. Both sequences induced apoptosis as evident from fluorescence staining. Flow cytometric analysis of 29 with the DMS79 cell line showed that the level of late apoptotic cells rose from 36% at 2 μM to 96% at 6 μM, compared to 25 that exhibited no effect. Efficacy of peptide 33 was separately evaluated in vivo using DMS79 xenografts. A low dose (1.5 mg/kg) was found to reduce tumour growth by ~ 30% (p < 0.05) at day 7, relative to the control group. Higher doses could not be used due to limited aqueous solubility. Furthermore, these peptides were shown to have improved stability. Exposed to neat mouse plasma for 48 hours, 29 and 35 remained intact by 68.5% and 81.0%, respectively, compared to 59.0% for 25 and 35.9% for 33. Complete metabolic stability of 29 and 35 was observed after 3 hours incubation in mouse S9 liver fraction. Aqueous solubility issues were overcome in feasibility studies incorporating 29 into liposomes for future in vivo efficacy testing. Finally, due to the high potency and stability of 29, a liposomal formulation of it may have a profound effect in in vivo efficacy studies against chemo-resistant SCLC.
15
Wong, Kenneth C. "Neuropeptide vascular reactivity in psoriasis". Thesis, The University of Sydney, 1998. https://hdl.handle.net/2123/27706.
Pełny tekst źródłaStreszczenie:
The skin is richly innervated with neuropeptide containing sensory nerve fibres
which are involved in cutaneous inflammatory responses and augmentation of
inflammation in the axonal reflex. Substance P (SP) and calcitonin generelated
peptide (CGRP) are two of the most abundant neuropeptides in the skin.
Neuropeptides have been postulated to play a role in the pathogenesis of
psoriasis. Evidence to suggest this include: elevated levels of neuropeptides in
psoriatic lesions; exacerbation of the disease with stress; improvement of
psoriatic lesions with topical capsaicin, which is known to deplete SP from
sensory neurons; and clearing of psoriatic plaques when the cutaneous nerve
supply is severed.
Previous work by Artemi et al. determined that the vascular response to
intradermal CGRP in nonlesional psoriatic skin (> 5 cm from lesions) was
similar to that in the skin of normal subjects. However in one subject with
extensive psoriasis in whom all neuropeptide injections were less than 5 cm
from lesional skin, there were exaggerated responses to neuropeptide (CGRP)
injections. This raised the possibility that perilesional psoriatic skin may have
an inherently abnormal vascular response to neuropeptides such as CGRP.
This thesis investigated the cutaneous vascular response to intradermal
injections of CGRP in nine and SP in ten subjects with chronic plaque type
psoriasis. In each subject the effect of two doses of intradermally injected
CGRP and SP on skin blood flow in perilesional (clinically normal skin up to 1
cm from the lesion) and nonlesional skin (clinically normal skin at least 5 cm
from the nearest lesion) was measured using laser Doppler flowmetry.
CGRP and SP caused dose-dependent increases in cutaneous blood flow in
both perilesional and nonlesional psoriatic skin, which was not statistically
different between the two injection sites. Mean values for pro-injection
cutaneous blood flow were higher in perilesional than nonlesional skin. This
study has shown that the cutaneous vasculature in perilesional skin is not
inherently different from nonlesional psoriatic skin in its response to
intradermal injections of CGRP and SP.
16
Morgat, Clément. "Imagerie des récepteurs de neuropeptides pour le ciblage tumoral". Thesis, Bordeaux, 2015. http://www.theses.fr/2015BORD0308/document.
Pełny tekst źródłaStreszczenie:
Des récepteurs de neuropeptides peuvent être fortement exprimés à la surface descellules tumorales offrant ainsi l’opportunité de les visualiser en imagerie par Tomographie d'Emissionde Positons (TEP) grâce à des analogues radiomarqués au 68Ga, 64Cu ou au 18F, mais également desélectionner des patients répondeurs à une radiothérapie métabolique à l'aide de ces mêmes analogues,radiomarqués au 177Lu ou 90Y. Un exemple phare a été le développement d’analogues radiomarqués dela somatostatine pour l'imagerie (68Ga-DOTATOC) et le traitement (177Lu-DOTATATE) des tumeursneuro-endocrines (TNE). Cette voie diagnostique et thérapeutique s’est récemment amplifiée avecl’identification d'autres neuropeptides et leurs récepteurs (sur)exprimés par les cellules tumorales. Cetravail de Thèse s'est donc déroulé selon plusieurs thématiques dont la première a été la mise en placed'une plate-forme de radiomarquage au 68Ga (une des premières en France) pour introduire l'imageriedes récepteurs somatostatine dans les TNE à Bordeaux (essai clinique GALTEP utilisant le 68Ga-DOTATOC) ou d'autres molécules innovantes (68Ga-PSMA dans le cancer de la prostate). Afind’envisager d'autres applications des récepteurs de la somatostatine nous avons recherché leurexpression dans des lymphomes de Hodgkin. Enfin, nous nous sommes concentrés sur ledéveloppement de deux autres familles de neuropeptides; les récepteurs de la bombésine (GRP-R etNMB-R) et de la neurotensine (NTR1). Nous avons finement caractérisé l'expression du GRP-R dansle cancer du sein et développé une nouvelle classe de radiopeptides pour le ciblage des récepteurs de labombésine. Enfin, nous avons étudié NTR1 dans diverses tumeurs pour fournir le rationnel nécessaireau développement d'analogues de la neurotensineNeuropeptide receptors can be highly expressed on the cell surface of tumor cells,paving the way to their visualization with Positron Emission Tomography (PET) using analoguesradiolabeled with 68Ga, 64Cu or 18F, but also to select patients who can benefit fromradiopharmaceutical therapy using similar analogues radiolabeled with 177Lu or 90Y. An example hasbeen the development of somatostatin radio-analogues for imaging (68Ga-DOTATOC) and therapy(177Lu-DOTATATE) of neuroendocrine tumors (NET). This concept has gained insight since thediscovery of other neuropeptides and their receptors (over)expressed on diverse tumors. This PhD hasbeen conducted according to several axis, the first being the establishment of a 68Ga-radiolabelingplatform (among the first in France) to introduce somatostatin receptor PET imaging of NET inBordeaux (clinical trial GALTEP using 68Ga-DOTATOC) but also other innovative molecules (68Ga-PSMA for prostate cancer imaging). Furthermore, to consider other applications of somatostatinreceptors we investigated their expression in Hodgkin's lymphomas. We then mainly aimed atinvestigating possibilities offered by two other families of neuropeptide receptors: bombesin receptors(GRP-R and NMB-R) and neurotensin receptors (NTR1). For the bombesin family, we have wellcharacterized GRP-R expression in breast cancer and developed a novel class of radiopeptide forbombesin receptors targeting. Finally, we studied NTR1 expression in various tumors (notably prostatecancer) to provide molecular basis necessary for the development of neurotensin analogues
17
Ehrström, Marcus. "Studies on the effect of orexin on upper gastrointestinal function in rats and man /". Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-957-9/.
Pełny tekst źródła
18
Dadgar, Anoushiravan. "Studies on rat gastrointestinal neuropeptide Y". Thesis, University of British Columbia, 1989. http://hdl.handle.net/2429/27410.
Pełny tekst źródłaStreszczenie:
A sensitive and specific radioimmunoassay (RIA) for Neuropeptide Y (NPY) was developed and quantitation, characterization and release studies were performed.
The development of the RIA required the purification of the NPY tracer due to both multiple iodinated products resulting from the five tyrosine residues in its amino acid sequence, and the presence of unlabelled NPY. Ion-exchange and reverse phase high performance chromatography (HPLC) purification of ¹²⁵I-NPY were performed. Optimal purification of ¹²⁵I-NPY was achieved using a HPLC with a μBondapak C₈ column and a 45-50% acetonitrile concentration gradient. A polyethylene glycol separation technique was used in conjunction with the HPLC purified tracer to improve assay conditions.
Although many studies aimed at elucidating the actions of NPY have been performed, little information is available on the distribution of gastrointestinal (GI) NPY in the rat. Therefore the NPY-immunoreactivity (IR) in extracts of the various regions of the GI tract were determined using the developed RIA. The tissue content of NPY was found to be highest in the various segments of the rat stomach, with a decreasing trend in NPY-IR down the GI tract until the level of the ascending colon where an increase was detected. Characterization studies on the tissue extracts were performed using gel filtration chromatography and HPLC. One immunoreactive species was detected in the corpus and ileum extracts using gel filtration chromatography, and in the corpus and colon extracts using HPLC. This immunoreactive species eluted in a position similar to synthetic porcine NPY and later than peptide YY (PYY).
In the physiological investigation of the the role of neuropeptides in the regulation of GI functions, release studies are crucial. The presence of high levels of NPY-IR in the stomach allowed the investigation of the release mechanisms of NPY in the perfused isolated rat stomach. However, due to the low basal secreted levels of NPY in comparison with other gastric peptides, as well as the enzymatic degradation and/or peptide uptake that occurs in the stomach vasculature, certain steps had to be taken to allow for the detection of the endogenously released peptide. Sep Pak extraction was found to be required to concentrate the endogenously released peptide. Proteolytic inhibitors were also added to the perfusate to reduce enzymatic degradation. A low basal level of NPY was detected which ranged from 98 to 147 fmole/min. Neuropeptide Y was found to be released into the gastric vasculature in response to high potassium depolarization.
A few studies have been performed on cholinergic effects on NPY release, however no direct release studies have been performed on NPY-containing neurones innervating the stomach. Therefore, the actions of cholinergic agonists and antagonists on NPY secretion in the isolated perfused rat stomach were investigated. Acetylcholine and the nicotinic ganglionic agonist dimethyl-phenyl-piperazinium (DMPP) stimulated NPY secretion. The acetylcholine-stimulated secretion was not blocked by the cholinergic muscarinic antagonist atropine and was partially blocked by the ganglionic cholinergic antagonist hexamethonium.
The effects of α- and β-adrenergic agonists and antagonists on NPY secretion into the stomach vasculature were investigated in order to elucidate possible adrenergic release mechanisms. There were conflicting results on the α-adrenergic release of NPY. Both the α-adrenergic antagonist phentolamine and the agonist phenylephrine had a stimulatory effect on NPY secretion in the stomach. The β -adrenergic agonist isoproterenol had a stimulatory effect on NPY release. The β -adrenergic antagonist propranolol caused an initial small increase in mean NPY levels followed by a decrease, but this was not found to be statistically significant.
These studies demonstrated the presence of NPY in the GI tract of the rat with the highest content being in the rat stomach. There are cholinergic stimulatory mechanisms involved in the secretion of NPY which are partially ganglionically mediated. The results did not conclusively demonstrate as to whether there is an α-adrenergic stimulatory or
inhibitory action on NPY-containing neurones in the gut, however preliminary release studies suggest there is a β-adrenergic stimulatory mechanism involved in NPY secretion.Medicine, Faculty of
Cellular and Physiological Sciences, Department of
Graduate
19
Poole, Sarah Louise. "Neuropeptide modulation of medullary autonomic circuits". Thesis, University of Leeds, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.434147.
Pełny tekst źródła
20
Burnet, Philip William John. "Studies on a novel neuropeptide, cerebellin". Thesis, Imperial College London, 1989. http://hdl.handle.net/10044/1/47371.
Pełny tekst źródła
21
Nunes, Ana Filipa Duarte. "Influence of transthyretin on neuropeptide processing". Doctoral thesis, Instituto de Ciências Biomédicas Abel Salazar, 2007. http://hdl.handle.net/10216/7209.
Pełny tekst źródła
22
Choi, Yohan. "Neuropeptide Y in early kidney development". Diss., [La Jolla, Calif.] : University of California, San Diego, 2009. http://wwwlib.umi.com/cr/ucsd/fullcit?p3344676.
Pełny tekst źródłaStreszczenie:
Thesis (Ph. D.)--University of California, San Diego, 2009.Title from first page of PDF file (viewed March 18, 2009). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references (p. 146-154).
23
Nunes, Ana Filipa Duarte. "Influence of transthyretin on neuropeptide processing". Tese, Instituto de Ciências Biomédicas Abel Salazar, 2007. http://hdl.handle.net/10216/7209.
Pełny tekst źródła
24
Duroux, Stéphane. "Neuropeptides et muqueuse nasale". Bordeaux 2, 1994. http://www.theses.fr/1994BOR23014.
Pełny tekst źródła
25
Phan, Toan Anh. "Ocular immunomodulating neuropeptides alpha-MSH and neuropeptide Y modulate phagocytic activity of the microphage cell line RAW 246.7". Thesis, Boston University, 2012. https://hdl.handle.net/2144/12591.
Pełny tekst źródłaStreszczenie:
Thesis (M.A.)--Boston University
PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.The eye is an immune privileged tissue. Within the ocular microenvironment, there are regulatory mechanisms that suppress inflammation. These anti-inflammatory mechanisms are partly mediated by immunomodulating neuropeptides. We previously found that alpha-melanocyte stimulating hormone (α-MSH) and Neuropeptide Y (NPY) together induce activation of myeloid suppressor-like macrophages. In this study, we examined the possibility that α-MSH and NPY also modulate phagocytosis by macrophages. The monocytic cell line RAW 246.7 was treated with α-MSH and NPY at 1 ng/ml each, a concentration produced by retinal pigment epithelial cells in culture. The treated cells were fed florescent bioparticles of Gram(-) E. Coli or Gram(+) S. Aureus with or without opsin and assayed by flow cytometry. Also tested were the formation of phagolysosomes using pH sensitive florescent E. Coli or S. Aureus bioparticles with or without opsin, and the level of mannose receptors. The a MSH and NPY treated macrophages were significantly suppressed in their capacity to phagocytize unopsonized E. coli; however, suppression of S. Aureus phagocytosis was limited to NPY treated macrophages. In addition, α-MSH and NPY co-treatment suppressed phagocytosis and phagolysosome formation in the macrophages. Fluorescent microscopy imaging showed that there was a qualitative change in phagolysosome formation in opsonized bioparticle conjugates corresponding to the change seen in relative intensity measurements. There was no significant change in the number of man nose receptors in α-MSH, NPY, or α-MSH and NPY treated cells. As α-MSH and NPY together can induce suppressor macrophages within the ocular microenvironment, they can also modulate in a stimulus-dependent manner phagocytic signals within the macrophages. Therefore while the eye is protecting itself from the damaging effects of inflammation it may be making itself vulnerable by having less than optimal innate immune clearance of infectious pathogens.
26
Eckard, Christophe. "Characterisation of neuropeptide Y receptors by antibodies /". [S.l.] : [s.n.], 1999. http://e-collection.ethbib.ethz.ch/show?type=diss&nr=13120.
Pełny tekst źródła
27
Fälth, Savitski Maria. "Improved Neuropeptide Identification : Bioinformatics and Mass Spectrometry". Doctoral thesis, Uppsala universitet, Institutionen för farmaceutisk biovetenskap, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-9400.
Pełny tekst źródłaStreszczenie:
Bioinformatic methods were developed for improved identification of endogenous peptides using mass spectrometry. As a framework for these methods, a database for endogenous peptides, SwePep, was created. It was designed for storing information about endogenous peptides including tandem mass spectra. SwePep can be used for identification and validation of endogenous peptides by comparing experimentally derived masses of peptides and their fragments with information in the database. To improve automatic peptide identification of neuropeptides, targeted sequence collections that better mimic the peptidomic sample was derived from the SwePep database. Three sequence collections were created: SwePep precursors, SwePep peptides, and SwePep predicted. The searches for neuropeptides performed against these three sequence collections were compared with searches performed against the entire mouse proteome, and it was observed that three times as many peptides were identified with the targeted SwePep sequence collections. Applying the targeted SwePep sequence collections to identification of previously uncharacterized peptides yielded 27 novel potentially bioactive neuropeptides. Two fragmentations studies were performed using high mass accuracy tandem mass spectra of tryptic peptides. For this purpose, two databases were created: SwedCAD and SwedECD for CID and ECD tandem mass spectra, respectively. In the first study, fragmentation pattern of peptides with missed cleaved sites was studied using SwedCAD. It was observed that peptides with two arginines positioned next to each other have the same ability to immobilize two protons as peptides with two distant arginines. In the second study, SwedECD was used for studying small neutral losses from the reduced species in ECD fragmentation. The neutral losses were characterized with regard to their specificity and sensitivity to function as reporter ions for revealing the presence of specific amino acids in the peptide sequence. The results from these two studies can be used to improve identification of both tryptic and endogenous peptides. In summary, a collection of methods was developed that greatly improved the sensitivity of mass spectrometry peptide identification.
28
Pearce, Craig M. "Central neuropeptide Y control of gastric function". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/nq24554.pdf.
Pełny tekst źródła
29
Broberger, Christian. "Neuropeptide circuitries regulating food and water intake /". Stockholm, 1999. http://diss.kib.ki.se/1999/91-628-3625-0/.
Pełny tekst źródła
30
Price, John Stephen. "Receptor binding and metabolism of neuropeptide Y". Thesis, University of Cambridge, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.335180.
Pełny tekst źródła
31
Hamdan, Suhail A. El-Ghani. "The neuropeptide ACTH and the immune system". Thesis, University of Strathclyde, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.366747.
Pełny tekst źródła
32
Xu, Isabella Shi. "The role of neuropeptides in spinal nociceptive mechanisms with special emphasis on galanin, neuropeptide Y and orphanin FQ/nociceptin /". Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-3973-X/.
Pełny tekst źródła
33
Lin, Ming. "Identification and functional characterization of relaxin-type and pedal peptide/orcokinin-type neuropeptides in the starfish Asterias rubens". Thesis, Queen Mary, University of London, 2017. http://qmro.qmul.ac.uk/xmlui/handle/123456789/30715.
Pełny tekst źródłaStreszczenie:
Neuropeptides are neuronal signaling molecules that regulate many physiological and behavioural processes in vertebrates and invertebrates. Investigation of neuropeptide signaling in echinoderms (e.g. starfish) can provide insights into the evolution of neuropeptide systems because as deuterostomian invertebrates they occupy an "intermediate" phylogenetic position between vertebrates and protostomian invertebrates. Recent analysis of neural transcriptome data from the starfish Asterias rubens has identified 40 transcripts encoding neuropeptide precursors. Here the expression and function of neuropeptides derived from four of these precursors was investigated: relaxin-like gonad-stimulating peptide precursor (AruRGPP), relaxin-like peptide precursor 2 (AruRLPP2), pedal peptide-like neuropeptide precursors 1 and 2 (ArPPLNP1 and ArPPLNP2). AruRGP induces spawning of ovarian fragments from A. rubens. Analysis of the expression of AruRGPP in A. rubens using mRNA in situ hybridization revealed expression by cells in the radial nerve cords, circumoral nerve ring and tube feet. Furthermore, a band of AruRGPP-expressing cells was also identified in the body wall epithelium lining the cavity that surrounds the sensory terminal tentacle and optic cushion at the tips of the arms. Discovery of these cells is important because they are candidate physiological mediators for hormonal control of starfish spawning in response to environmental cues. Interestingly, AruRLPP2 is also expressed in the same region of the arm tip as AruRGPP but the physiological role(s) of AruRLP2 is not yet known. Analysis of the expression of ArPPLNP1 and ArPPLNP2 using mRNA in situ hybridization revealed a widespread pattern of expression in A. rubens. Furthermore, immunohistochemical localization of peptides derived from these precursors revealed immunostaining in neuronal processes innervating muscles. Consistent with this pattern of expression, peptides derived from ArPPLNP1 and ArPPLNP2 act as muscle relaxants in starfish. Interestingly, this contrasts with previous findings from protostomian invertebrates, where pedal peptide/orcokinin-type neuropeptides act as muscle contractants.
34
Pickavance, Lucy Cecilia. "Somatostatin, neuropeptide Y and galanin: Immunohistochemical detection and mapping of neuropeptide distributions in goldfish brain, with reference to rat". Thesis, University of Ottawa (Canada), 1990. http://hdl.handle.net/10393/5626.
Pełny tekst źródłaStreszczenie:
The biochemical neuroanatomy of the goldfish brain, with some reference to that in the rat brain, was investigated. Retrograde tracing immunofluorescence techniques reveal that the efferents of the somatostatin (SRIF)-positive cells of the entopeduncular nucleus of the rat do not project to the ventroanterior/ventrolateral nuclei of the thalamus. Using of immunohistochemical staining techniques, the distributions of the neurotransmitters SRIF, NPY and galanin (Gal) were mapped throughout the brain of the goldfish. Single-label immunohistochemistry was used to determine the distribution of Gal in the goldfish brain. Gal is present primarily in fibres and terminals but in only a few cell bodies restricted to the preoptic and tuberal hypothalamus and the reticular formation. When the distributions of SRIF, NPY and Gal in the goldfish brain were compared to the literature on brains of other teleost fish and in the mammalian brain, it was clear that they have altered little across species. (Abstract shortened by UMI.)
35
Guo, Ningning. "GSH : a new candidate neuropeptide in the CNS". Thesis, University of British Columbia, 1991. http://hdl.handle.net/2429/29856.
Pełny tekst źródłaStreszczenie:
The physiological significance of glutathione (GSH) in the mammalian central nervous system is still uncertain, although some evidence has indicated that GSH may play an important role in the CNS.
To address the question of whether GSH may be a candidate for a neuropeptide in the CNS, one step is to establish that GSH receptors are present.
In the present study, biotinyl-GSH was synthesized and purified to detect the GSH receptor in the CNS. Histochemical experiments showed that GSH binding sites appeared on the white matter ( such as cingulum, dorsal hippocampal commissure, cerebral peduncle, fasciculus retrbflexus, mammillothalamic tract etc.) of the rat brain. It thus suggested that the GSH receptors might be on astrocytes or oligodendrocytes. Radioactive receptor assays were performed on cultured astrocytocytes using [³⁵S]GSH. Scatchard analysis revealed two binding sites of K₁ = 4.67±0.75 nM, Bmax₂ =70±9.2 fmoles / 6.4 x10⁵ cells (or Bmax₁=6.6 x10⁴molecules / cell), Kd₂=35.14±2.1 nM, Bmax₂=260±12.77 fmole / 6.4 x10⁵ cell (or Bmax₂ = 2.4 x10⁵ molecules / cell). The association and dissociation kinetics studies gave a K₊₁ of 0.003nM⁻¹min¹, and a K₋₁ of 0.0168 min⁻¹for site I. These rate constants gave a K₁ of 5.6 nM, consistent with that from Scatchard analysis. Colloidal gold technique and immunofluorescence double staining also showed the GSH binding sites on cultured astrocytes, and suggested that the binding sites might be GSH receptors.
The present study is the first to report the presence of GSH receptors on astrocytes. Based on receptor binding assays and cytochemical experiments, this study not only depicts the biochemical characteristics of GSH receptors in the brain, but also shows the receptor at the cellular level. These results support the view that GSH might be a neuroactively signal substance in the CNS.Medicine, Faculty of
Graduate
36
Salaneck, Erik. "Molecular Evolution of Neuropeptide Y Receptors in Vertebrates". Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2001. http://publications.uu.se/theses/91-554-4988-3/.
Pełny tekst źródła
37
Zachrisson, Olof. "On the neuropeptide mRNA expression following neuropsychopharmacological treatments /". Stockholm, 1998. http://diss.kib.ki.se/search/diss.se.cfm?19980925zach.
Pełny tekst źródła
38
Morales, Medina Julio. "Role of neuropeptide Y in emotional dysfunctional conditions". Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=107774.
Pełny tekst źródłaStreszczenie:
Anxiety and depression are two highly debilitating disorders with high prevalence and co-morbidity with other mental and physical disorders. Current available treatments for these diseases present major caveats, thus the search for novel targets of treatment are the foremost challenges in health research. In this regard, the neuropeptide Y (NPY) system has emerged as a neuromodulator of emotional processing. This peptide mediates its effects by acting on its Y1, Y2 and Y5 receptor subtypes in the brain. However the contribution of each receptor subtype in emotional processes is still not clear, given their differential distribution in the brain as well as in the neuronal synapse. Therefore, the aim of the present study was to dissect the role of each of these receptor subtypes in animal models of emotional dysfunctional conditions. Of particular interest were, the Y1 agonist, Y2 antagonist as well as Y5 agonist as the mediators of emotional dysfunctional conditions. To investigate this, first we fully characterized an animal model of depression and anxiety, the olfactory bulbectomized (OBX) model. Following this characterization we observed that the administration of Y Y1-agonist reversed hyperlocomotion in open field test (OFT), reduced immobility time in the forced swim test (FST) and increased contacts in the social interaction test (SIT) in OBX rats, however, no effect was observed in corticosterone (CORT)-induced anxiety model. In addition, the Y2 antagonist decreased immobility in the FST in the OBX rat while increased social contacts in sham animals. Interestingly, this compound also induced an anxiolytic-related effect in CORT-treated rats. Meanwhile, the Y5 agonist decreased locomotion in OF and increased contacts in the SI test in the OBX rat, induced an anxiolityc-related effect in CORT-treated animals and increased body weight in control animals. Taken together, these results indicate that the treatment with molecules targeting different NPY receptor subtypes modulate different traits of anxiety and depression. In addition, antagonism of Y2 receptors elicits a potent effect regardless of the mental state of the animal while the treatment with Y1 or Y5 agonists induces differential effects depending on the situation. Thus, targeting these NPY receptors may be of pharmacotherapeutic relevance in the treatment of some forms of anxiety and depression in humans.L'anxiété et la dépression sont deux désordres émotionnels ayant un impact socio-économique majeur. Ils présentent une haute prévalence et co-morbidité avec d'autres désordres mentaux et physiques. Actuellement, les traitements disponibles contre ces maladies possèdent de nombreuses contre-indications. La découverte de nouvelles cibles de traitements est donc un défi crucial dans la recherche en santé mentale. Le neuropeptide Y (NPY) est un neuromodulateur des processus émotionnels. Ce peptide exerce son action dans le cerveau via divers récepteurs incluant les sous-types Y1, Y2 et Y5. La contribution de chacun de ces récepteurs n'est cependant pas claire, et leur distribution varie aussi bien quant à leur localisation pré- ou post-synaptique que régionale. Le but de cette thèse est donc de préciser le rôle de chacun des récepteurs du NPY dans des modèles animaux de dysfonctions émotionnelles. Un intérêt particulier est porté sur les agonistes et antagonistes des récepteurs Y1, Y2 et Y5. Nous avons, dans un premier temps, caractérisé en détail un modèle animal de dépression et d'anxiété: le modèle de la lésion du bulbe olfactif (OBX). Par la suite, nous avons observé que l'administration d'un agoniste Y1 renverse l'hyperlocomotion lors du test 'open field (OF), réduit le temps d'immobilité dans le test de nage forcée (forced swim test, FST) et enfin, augmente les interactions entre les animaux lors du test d'interactions sociales (social interaction, SI) et ce, spécifiquement chez les rats OBX. Cependant, aucun n'effet n'a été observé dans un autre modèle ou l'anxiété est induite suite à l'injection de la corticostérone. Un antagoniste Y2, quant à lui, diminue l'immobilité lors du test FST chez les rats OBX alors qu'il augmente les interactions sociales seulement chez les animaux contrôles. Fait intéressant, ce composé induit aussi un effet anxiolytique chez les rats traités à la corticostérone. Enfin, un antagoniste Y5 diminue l'activité locomotrice dans l'OF, augmente les interactions lors du test SI chez les rats OBX, induit la sédation chez les animaux traités à la corticostérone et augmente le poids des animaux contrôles. Ces résultats indiquent que le traitement avec des molécules ciblant différentes classes de récepteurs du NPY pourraient circonscrire spécifiquement certains symptômes de l'anxiété et de la dépression. De plus, un antagoniste du récepteur Y2 semble capable de moduler les comportements anxieux et dépressifs alors que les agonistes Y1 et Y5 induisent des effets différentiels dépendamment du contexte. Ainsi, les récepteurs du NPY pourraient s'avérer être des cibles pharmaceutiques pertinentes pour le traitement de certaines formes d'anxiété et de dépression.
39
Chaloin, Olivier. "Synthèse d'analogues peptidiques et pseudopeptidiques du neuropeptide Y". Montpellier 2, 1996. http://www.theses.fr/1996MON20100.
Pełny tekst źródłaStreszczenie:
Ce travail est consacre a la synthese d'analogues peptidiques et pseudopeptidiques du neuropeptide y. Une etude sur les relations structure-activite a ete developpee. Dans un premier temps, nous avons synthetise des analogues modifies au niveau du pentapeptide c terminal par des substitutions d'aminoacides et introduction de liaisons pseudopeptidiques. Dans une deuxieme partie, nous avons synthetise des analogues dimerises de la partie c terminale du neuropeptide y. La derniere partie de ce travail a ete la synthese d'analogues du bibp 3226, un puissant antagoniste selectif des recepteurs y1 du neuropeptide y. La substitution de certains residus du bibp 3226 a permis de conduire a des composes peptidomimetiques selectifs des recepteurs y1. L'activite biologique de chacun des analogues synthetises a ete evaluee in vitro sur differentes preparations pour conduire a des composes agonistes ou antagonistes du neuropeptide y
40
GELOT, AGATHE. "Neuropeptide ff et nociception ; role des systemes opioides". Toulouse 3, 1998. http://www.theses.fr/1998TOU30190.
Pełny tekst źródłaStreszczenie:
Les systeme neuropeptide ff (npff) est un systeme neuronal a part entiere compose de voies neuronales et de recepteurs specifiques. Le npff module les sytemes opioides de facon complexe, activites pro- ou anti-opioides, suivant des modalites encore peu connues. Le but de ce travail est de caracteriser le systeme npff au plan pharmacologique chez la souris a l'aide de deux analogues ayant des proprietes differentes et d'etudier ses modalites de fonctionnement chez des animaux traitees chroniquement par les opioides. Pour cela nous avons recherche 1) les relations entre le npff et differents types d'analgesies opioides (endogene et exogene) ; 2) un mecanisme d'action possible des proprietes hypothermisantes et anti-opioide du npff ; 3) les effets d'un traitement chronique par la morphine sur differentes composantes du systeme npff (proprietes pharmacologiques, recepteurs, peptides). Ce travail a permis de montrer que 1) les effets des deux analogues du npff utilises (le 1dme et le 3d) suggerent l'existence de plusieurs effecteurs du npff (soit plusieurs recepteurs, soit plusieurs seconds messagers) ; 2) le npff participe tres clairement au developpement de la tolerance et de la dependance a la morphine. Ce travail met en evidence la capacite du systeme npff a engendrer des effets pro- ou anti-opioides en fonction de son niveau de stimulation et des proprietes etudiees. Il a egalement permis d'etablir un modele d'interaction entre les differents peptides permettant d'etudier le npff et les recepteurs du npff, afin de mieux comprendre les differents effets de ce peptide au sein du snc et vis-a-vis des opioides.
41
Marco, Heather G. "Neuropeptide hormones from the eyestalks of Jasus Lalandii". Doctoral thesis, University of Cape Town, 2000. http://hdl.handle.net/11427/7692.
Pełny tekst źródłaStreszczenie:
Bibliography: p. 242-264.The X-organ sinus gland complex, situated in the eyestalks of decapod crustaceans, are known to be a source of a variety of neuropeptide hormones that regulate a number of diverse physiological processes. This neuroendocrine complex was investigated in 3 crustacean species, viz. the European shore crab Carcinus maellas, and 2 spiny lobster species Jasus lalandii and Panulirus homarus by means of tissue immunocytochemistry and an enzyme-linked immunosorbent assay (ELISA). Positive immunoreactions, associated with the X-organ - sinus gland system only, were obtained with antisera raised against crustacean hyperglycaemic hormone (cHH) of the American lobster (Homarus americanus), the Mexican crayfish (Procambarus bouvieri) and the edible crab (Cancer pagurus), as well as with antisera raised against vitellogenesis-inhibiting hormone (VIH) of the H. americanus and moult-inhibiting hormone (MIH) of C. pagurus. This is the first time that the immunolocalisation of these 3 hormones have been studied in a single crustacean species. The chief results of this comparative immunocytochemical study showed that (1) neuropeptide hormones of the shore crab and the 2 spiny lobster species were sufficiently homologous in primary structure to be recognised by the heterologous antisera, thus, an indication of conserved peptide structures across the species and infraorder boundaries; (2) preabsorbed complexes of purified peptides and antisera from the edible crab did not produce any immunoreactions in tissue immunocytochemistry, nor in ELISA, thus, indicating the specificity of the anti-cHH and anti-MIH sera; (3) the anti-VIH serum demonstrated the ability to bind epitopes on cHH and MIH peptides and is, thus, not a specific antiserum in this study; (4) there is co-localisation of cHH, MIH, VIH immunoreactivity in the eyestalk neuroendocrine complexes of all 3 species studied which suggests that the different peptide hormones can be synthesized in the same neuronal cell bodies. This co-localisation of neuropeptides in the eyestalk of J lalandii was confirmed by a double-staining immunoflourescence experiment, and finally (5) immunoreactivity of antisera raised against cHH of H. americanus and MIH of C. pagurus was associated with distinct and unique peak fractions, following reverse-phase high pressure liquid chromatographic (RP-HPLC) separation of sinus gland extracts from J. lalandii. A total of 6 neuropeptide hormones belonging to the cHH/MIH/VIH peptide family were isolated, functionally characterised and sequenced from extracts of sinus glands from the South African west coast rock lobster, Jasus lalandii. This is the first complete report on these peptides from any species belonging to the Palinuridae infraorder.
42
EATON, KATHERINE L. "NEUROPEPTIDE RECEPTORS IN THE AMYGDALA: RELEVANCE TO STRESS". University of Cincinnati / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1193098999.
Pełny tekst źródła
43
Eaton, Katherine L. "Neuropeptide receptors in the amygdala relevance to stress /". Cincinnati, Ohio : University of Cincinnati, 2007. http://rave.ohiolink.edu/etdc//view?acc_num=ucin1193098999.
Pełny tekst źródłaStreszczenie:
Thesis (Ph.D.)--University of Cincinnati, 2007.Advisor: Dr. Floyd R Sallee. Title from electronic thesis title page (viewed Mar. 29, 2009). Keywords: amygdala; neuropeptide; NPY receptor; CRH receptor; chronic stress; glucocorticoid; GIR. Includes abstract. Includes bibliographical references.
44
Krause, Katharina Isabelle [Verfasser]. "Neuropeptide und Lipide der Haut / Katharina Isabelle Krause". Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2009. http://d-nb.info/1023817861/34.
Pełny tekst źródła
45
DEL, ZOPPO Luisa. "Analoghi del Neuropeptide S modificati in posizione 5". Doctoral thesis, Università degli studi di Ferrara, 2013. http://hdl.handle.net/11392/2388923.
Pełny tekst źródłaStreszczenie:
Neuropeptide S (NPS) is the last neuropeptide identified via Reverse Pharmacology techniques.
NPS selectively binds and activates a previously orphan GPCR 154, now named NPSR, producing
intracellular calcium mobilization and cAMP levels. Biological functions modulated by the
NPS/NPSR system include anxiety, arousal, locomotion, food intake, memory, and drug addiction.
The primary sequence of NPS (in humans SFRNGVGTGMKKTSFQRAKS) is highly conserved
among vertebrates especially at the N-terminus. Ala- and D-scan together with truncation studies
demonstrated that the N-teminal sequence of the molecule is crucial for biological activity. Focused
structure–activity investigations performed on Phe2, Arg3, and Asn4 confirmed this indication and
revealed the chemical requirements of these positions for NPSR binding and activation. The
sequence Gly5-Val6-Gly7 seems to be important for shaping the bioactive conformation of the
peptide. Structure–activity studies on Gly5 enabled identification of the first generation of
peptidergic NPSR pure antagonists including [D-Cys(tBu)5]NPS and [D-Val5]NPS whose
antagonist properties were confirmed in vivo.
This PhD thesis is focused on the structure activity relationship study of NPS position 5. In
particular, in order to identify new potent and selective antagonists of the NPSR receptor, we have
designed, synthesized and inserted in position 5 of NPS the following non natural amino acids: i)
the chimeric Valine/Leucine amino acid, Ipv, 2-amino-3,3,4-trimethyl-pentanoic acid as racemate;
ii) the R and S form of the amino acid, Ddb, 2,4-diamino-3,3-dimethylbutyric acid characterized by
a branched aliphatic side chain functionalized with a primary amino group; iii) some penicilammine
S-alkylate analogs.
This work has allowed to investigate and apply different chemical strategies for the synthesis of
alpha-amino acids characterized by branched aliphatic side chains. In addition the original synthetic
scheme adopted for the synthesis of 2-amino-3,3,4-trimethyl-pentanoic acid in which the key step is
the copper (I) chloride-catalyzed conjugated addition of i-propyl magnesium bromide to 2-
isopropylidene-malonic acid diethyl ester together with the commercial variety of Grignard reagents
available make this route suitable for further synthetic applications, including the synthesis of novel
non natural valine derivatives. The pharmacological data obtained further corroborate the proposal
that chirality and steric hindrance of position 5 of NPS are crucial chemical requirements for
modulating peptide efficacy and potency.
It has been also found that NPSR antagonists can be generated by replacing NPS position 5 with Damino
acids characterized by basic side chain. Finally, the use of S-alkyl penicilammine showed
that the increase in steric hindrance of position 5 is better tolerated if generated by an aromatic
substituent compared to aliphatic groups suggesting that planarity is a chemical feature useful for
the identification of novel NPSR antagonists.
46
Nagy, Dóra. "Peptidergic control of dormancy in Drosophila melanogaster". Doctoral thesis, Università degli studi di Padova, 2017. http://hdl.handle.net/11577/3426310.
Pełny tekst źródłaStreszczenie:
Organisms, especially those living in temperate zones, are constantly exposed to the cyclical changes of environmental factors due to the alternating seasons. In order to increase their chances of survival, they evolved different adaptive mechanisms to withstand the stress of harsh periods. Among insects, diapause is the most commonly used strategy to achieve seasonal synchronization.
Diapause is a neuro-hormonally regulated state of dormancy that enables insects to switch to an alternative developmental program when external conditions are not suitable for normal development. In the fruit fly, Drosophila melanogaster, diapause is characterized by the arrest of the ovarian development at previtellogenic stages. Insulin-like signaling has been identified as a key regulator of dormancy in many organisms. The insulin producing cells (IPCs), located in the Pars intercerebralis, are crucial neurosecretory cells that are neuroanatomically connected to the neuroendocrine center that governs hormonal regulation of diapause. They are responsible for the production and release of different insulin-like peptides that have been found to act as diapause-antagonist hormones. Here we found that two neuropeptides, pigment dispersing factor (PDF) and short neuropeptide F (sNPF), produced in a small subset of neurons (ventrolateral clock neurons, LNvs), modulate the diapause response of the flies, and this regulation is likely to exist via the IPCs. We discovered that an additional PDF-expressing neuron cluster in the tritocerebrum (PDF-Tri), previously shown to undergo apoptosis very early during adulthood, actually survives at cold temperatures and could be involved in cold-related functions. Interestingly, these PDF-Tri neurons were found to be synaptically connected to the IPCs in the cold.
Expression of genetically encoded sensors for the second messenger cAMP revealed that, IPCs respond to both synthetic neuropeptides PDF and sNPF. Surprisingly, they react with large cAMP increases to the co-application of the two peptides, raising the possibility of a synergistic effect between sNPF and PDF in controlling IPC activity. Since the detected cAMP responses are all abolished in PDF receptor mutant background, they seem to be regulated by PDFR. The study of two differently diapausing field lines highlighted marked differences between their PDF expression patterns, possibly related to diapause regulation.
When studying the general properties of D. melanogaster dormancy, we explored the relative relevance of some features of the experimental protocols used for diapause assays. While in the standard protocol flies are raised at temperatures in the range 23-25°C and exposed to diapause-inducing conditions starting from the adult stage, we investigated the effects of lower growing temperatures on diapause levels. We documented changes in diapause levels due to these altered settings, highlighting their importance in controlling dormancy. Additionally, adopting semi-natural light-dark profiles that better mimic outdoor conditions, strong photoperiodic diapause was observed, which was not detectable when simple rectangular light-dark regimes were used. Our findings should be considered in designing new protocols for diapause studies.Gli organismi, soprattutto quelli che vivono in zone temperate, sono costantemente esposti a variazioni cicliche di fattori ambientali a causa dell’alternarsi delle stagioni. Si sono evoluti diversi meccanismi di adattamento che permettono di resistere e superare i periodi sfavorevoli. Tra gli insetti, la diapausa è la più comune strategia usata per raggiungere la sincronizzazione stagionale. La diapausa è uno stato di dormienza, regolato a livello neurologico ed ormonale, che permette agli insetti di avviare un programma di sviluppo alternativo quando le condizioni ambientali non permettono un normale sviluppo. Nel moscerino della frutta Drosophila melanogaster, la diapausa si manifesta con l’arresto dello sviluppo delle ovaie nella frase previtellogenica. Segnali di tipo insulin-like sono stati identificati come regolatori chiave della dormienza in molti organismi. Le insulin-producing cells (IPCs) si trovano nella Pars intercerebralis, sono neuroanatomicamente connessi al centro neuroendocrino che controlla la regolazione ormonale della diapausa. Queste cellule sono responsabili della produzione e del rilascio di differenti insulin-like peptides che sono stati identificati come ormoni antagonisti della diapausa. Abbiamo scoperto che due neuropeptidi, pigment dispersing factor (PDF) e short neuropeptide F (sNPF), prodotti da un piccolo gruppo di neuroni chiamati ventrolateral clock neurons, regolano il processo della diapausa nei moscerini attraverso le IPCs. Inoltre, abbiamo osservato che un altro gruppo di neuroni che producono PDF nel tritocerebrum (PDF-Tri) e che si ritenevano strutture rapidamente eliminate per apoptosi nell’adulto, in realtà sopravvivono e persistono nell’adulto a basse temperature, suggerendo quindi un loro coinvolgimento in funzioni correlate con la resistenza al freddo. L’espressione di sensori genetically-encoded per il secondo messaggero cAMP, ha rilevato che le IPCs reagiscono ad entrambi i neuropeptidi PDF e sNPF. Sorprendentemente reagiscono con grandi aumenti di cAMP alla somministrazione dei due peptidi, suggerendo un effetto sinergico tra sNPF e PDF nel controllo dell’attività delle IPCs. Dal momento che le risposte cAMP sono state abolite nel background mutante per il recettore PDF, sembrano essere regolate dallo stesso. Lo studio di due diverse linee che manifestano differenze nel comportamento relativo alla diapausa ha evidenziato differenze marcate nell’espressione di PDF, potenzialmente collegata della regolazione della diapausa. Studiando le proprietà generali della diapausa in D. melanogaster, abbiamo esplorato l’importanza relativa di alcuni aspetti dei protocolli sperimentali usati per i saggi di diapausa. Mentre nel protocollo originale i moscerini vengono fatti sviluppare a temperature comprese nel range 23-25oC e quindi esposti a condizioni che inducono la diapausa solo a partire dallo stadio adulto, noi abbiamo studiato gli effetti sui livelli di diapausa dello sviluppo a temperature inferiori. Abbiamo documentato cambiamenti nei livelli di diapausa indotti da queste modifiche, sottolineando la loro importanza nel controllo della dormienza. Inoltre, adottando profili di luce-buio seminaturali, che mimano meglio le condizioni esterne, è stata osservata una diapausa altamente regolata dal fotoperiodo. Una risposta fotoperiodica non era stata rilevata in studi precedenti nei quali venivano utilizzati regimi di luce-buio rettangolari. I nostri risultati suggeriscono l’opportunità di disegnare nuovi protocolli, più rappresentativi delle condizioni naturali, per lo studio delle basi genetiche e fisiologiche della diapausa.
47
Chan, Pui-shan. "Effects of NPY-Y1 receptor activation or inhibition on free radical generation during in vitro or in vivo cerebral ischemia". Click to view the E-thesis via HKUTO, 2006. http://sunzi.lib.hku.hk/hkuto/record/B35760825.
Pełny tekst źródła
48
Sickinger, Marlene. "Neuropeptidgehalt der bovinen Labmagenwand in Abhängigkeit von Rasse und Verlagerungszustand". Giessen : VVB Laufersweiler, 2007. http://geb.uni-giessen.de/geb/volltexte/2007/4790/index.html.
Pełny tekst źródła
49
Spada, Janek, Christian Sander, Ralph Burkhardt, Madlen Häntzsch, Roland Mergl, Markus Scholz, Ulrich Hegerl i Tilman Hensch. "Genetic association of objective sleep phenotypes with a functional polymorphism in the neuropeptide S receptor gene". Universitätsbibliothek Leipzig, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-144927.
Pełny tekst źródłaStreszczenie:
Background: The neuropeptide S receptor (NPSR1) and its ligand neuropeptide S (NPS) have received increased attention in the last few years, as both establish a previously unknown system of neuromodulation. Animal research studies have suggested that NPS may be involved in arousal/wakefulness and may also have a crucial role in sleep regulation. The single nucleotide polymorphism (SNP) rs324981 in NPSR1 has begun to shed light on a function of the NPS-system in human sleep regulation. Due to an amino acid exchange, the T-allele leads to an increased sensitivity of the NPSR1. In the only genomewide association study to date on circadian sleep parameters in humans, an association was found between rs324981 and regular bedtime. However, the sleep parameters in this study were only measured by self-rating. Therefore, our study aimed to replicate these findings using an objective measure of sleep. Methods: The study included n = 393 white subjects (62–79 years) who participated in an actigraphic assessment for determining sleep duration, rest duration, sleep onset, rest onset and sleep onset latency. Genotyping of the SNP rs324981 was performed using the TaqMan OpenArray System. Results: The genotype at rs324981 was not significantly associated with rest onset (bedtime) or sleep onset (p = .146 and p = .199, respectively). However, the SNP showed a significant effect on sleep- and rest duration (p = .007 and p = .003,
respectively). Subjects that were homozygous for the minor T-allele had a significantly decreased sleep- and rest duration compared to A-allele carriers. Conclusion: The results of this study indicate that the sleep pattern in humans is influenced by the NPS-system. However, the previously reported association between bedtime and rs324981 could not be confirmed. The current finding of decreased sleep duration in T/T allele carriers is in accordance with studies in rodents reporting similar results after NPS application.
50
Stricker-Krongrad, Alain. "Recherches sur les fonctions orexigenes du neuropeptide y cérébral". Nancy 1, 1993. http://www.theses.fr/1993NAN10385.
Pełny tekst źródłaStreszczenie:
Le contrôle du comportement alimentaire est le résultat de l'intégration dans le système nerveux central d'informations multiples. Le système constitué du noyau arque et du noyau paraventriculaire est un circuit intrahypothalamique à neuropeptide y implique dans la régulation de la préférence alimentaire et de l'hyperphagie. La mise en évidence d'une libération de neuropeptide y dans ce dernier noyau montre que son action centrale peut être comprise comme associée et non pas dépendante des circuits monoaminergiques cérébraux dans la mise en œuvre des phénomènes impliques dans les fonctions orexigènes