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1

Brumovsky, Pablo R. "Neuropeptides, sensory neurons and pain modulation /". Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-442-2/.

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2

Duroux, Stéphane. "Neuropeptides et muqueuse nasale". Bordeaux 2, 1994. http://www.theses.fr/1994BOR23014.

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Pheng, Leng-Hong. "Caractérisation pharmacologique des récepteurs natifs du neuropeptide Y et de la nociceptine". Sherbrooke : Université de Sherbrooke, 2001.

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4

Diez, Margarita. "Neuropeptide expression in mouse disease models /". Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-514-x/.

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5

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.

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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 limité
The 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
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6

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/.

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7

Lodge, Daniel 1977. "Neuropeptides, anxiety and alcoholism". Monash University, Dept. of Pharmacology, 2002. http://arrow.monash.edu.au/hdl/1959.1/7706.

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8

Ostlere, Lucy Sinclair. "Neuropeptides in atopic dermatitis". Thesis, Queen Mary, University of London, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.267167.

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9

Di, Marzo V. "Neuropeptides and leukotriene biosynthesis". Thesis, Imperial College London, 1988. http://hdl.handle.net/10044/1/47024.

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10

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.

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11

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.

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12

Morgat, Clément. "Imagerie des récepteurs de neuropeptides pour le ciblage tumoral". Thesis, Bordeaux, 2015. http://www.theses.fr/2015BORD0308/document.

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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 neurotensine
Neuropeptide 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
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13

Appelgren, Anna. "Neuropeptides in temporomandibular joint arthritis /". Stockholm, 1999. http://diss.kib.ki.se/1999/91-628-3893-8/.

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14

Leung, Po Sing. "Studies on some molluscan neuropeptides". Thesis, Queen's University Belfast, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.333802.

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15

Dougan, P. M. "Molecular studies on platyhelminth neuropeptides". Thesis, Queen's University Belfast, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.391110.

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16

Marshall, Anna K. "Myoactive neuropeptides in Manduca sexta". Thesis, University of Bath, 1995. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.307029.

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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/.

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18

Duerr, Heike Edith. "Molecular characterisation of neuropeptides in echinoderms". Thesis, Royal Holloway, University of London, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.314294.

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19

Littlewood, Gillian Mary. "Characterisation of membrane peptidases inactivating neuropeptides". Thesis, University of Leeds, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.236308.

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20

Terry, Adrian Simon. "Studies on the biosynthesis of neuropeptides". Thesis, University of Cambridge, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.254521.

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21

Ferré, Guillaume. "Dynamique structurale de complexes RCPG - neuropeptides". Thesis, Toulouse 3, 2019. http://www.theses.fr/2019TOU30141.

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Les récepteurs couplés aux protéines G (RCPG) reconnaissent un ligand extracellulaire afin de transmettre l'information correspondante à l'intérieur de la cellule. Ils sont des acteurs prépondérants en physiologie ainsi que des cibles pharmacologiques majeures. Nous avons étudié deux RCPG dont les ligands endogènes sont des peptides. a) Le récepteur ĸ opioïde (KOP) qui reconnait la dynorphine. Ce récepteur joue un rôle fondamental dans la régulation de la douleur et des mécanismes de récompense (et donc dans l'addiction). La découverte, la pharmacologie et les relations structure - fonction de la dynorphine sont décrites dans cette thèse sous la forme d'une revue publiée en 2019 dans "Vitamins and Hormones". L'activité des RCPG est assurée par une dynamique conformationelle riche et la résonance magnétique nucléaire (RMN) est particulièrement adaptée pour l'étudier. Elle nécessite néanmoins le marquage isotopique de la protéine d'intérêt, or la plupart des études structurales utilisent des RCPG surexprimés en cellules d'insecte. Nous avons mis au point la production de KOP avec une stratégie d'expression chez E. coli, outil de choix pour le marquage isotopique. Le récepteur recombinant a été purifié puis renaturé en micelles de détergent et s'est avéré être fonctionnel pour la liaison de son ligand. Ce sera un outil de choix pour des études structurales et dynamiques par RMN. b) Le récepteur sécrétagogue de l'hormone de croissance (GHSR), qui est naturellement activé par la ghréline, une hormone peptidique digestive acylée impliquée dans l'appétit, la sécrétion de l'hormone de croissance et l'homéostasie du glucose. Les interactions peptide - RCPG sont mal connues au niveau structural en raison de la difficulté à cristalliser ces complexes. Utilisant un récepteur GHSR perdeutérié, produit dans E. coli et reconstitué en nanodisques lipidiques dans l'équipe de J.L. Banères (IBMM, Montpellier), nous avons utilisé différentes expériences de RMN (relaxation 15N, NOE transféré et STD) pour caractériser finement la structure et la dynamique de la ghréline liée à son récepteur. Nous avons ainsi mis en évidence le mécanisme par lequel la chaîne acyle en position 3 de la ghréline assure une reconnaissance spécifique par GHSR
G protein-coupled receptors (GPCR) recognize an extracellular ligand in order to transmit the corresponding information inside the cell. They are major players in physiology and predominant pharmacological targets. Here, we studied two GPCR for which the endogenous ligands are peptides. a) The ĸ opioid receptor (KOP), which recognizes dynorphin, and which is involved in the regulation of pain and reward mechanism (and thus in addiction). The discovery, pharmacology and structure - activity relationship of dynorphin are described in this manuscript as a review published in "Vitamins and Hormones" in 2019. GPCR activity requires a complex conformational dynamics and nuclear magnetic resonance (NMR) is an excellent technique allowing such characterization. However, it requires isotope labeling of the proteins of interest and most of GPCR structural studies used receptors expressed in insect cells. We produced KOP using an E. coli expression strategy, which is the tool of choice for isotope labeling. The recombinant receptor was successfully refolded in detergent micelles and was shown to be functional in terms of ligand binding. It offers new possibilities to study its structure and dynamics by NMR. b) The growth hormone secretagogue receptor (GHSR) is naturally activated by ghrelin, a digestive peptide hormone of 28 amino-acids residues. This hormone - receptor system is involved in a multitude of physiological process such as the regulation of food intake, growth hormone secretion and glucose homeostasis. However, structural information about peptide - GPCR interaction is sparse because of the difficulty in crystallizing such complexes. Using a perdeuterated receptor expressed in E. coli and refolded in lipid nanodiscs in the group of J.L. Banères (IBMM, Montpellier), we used several liquid state NMR techniques (15N relaxation, transferred NOE, saturation transfer difference) to characterize the 3D structure and dynamics of ghrelin bound to GHSR. Our work particularly shed the light on the role of a post-translational modification (acylation on Ser 3) on the receptor specific recognition mechanism
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Ho, Chi-wang John, i 何志泓. "Molecular characterization of chicken galanin and galanin receptor family". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B47752646.

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 Galanin is a multi-functional neuropeptide with widespread distribution in the central and peripheral nervous systems of different species. It exerts a broad spectrum of physiological functions through the interactions with three galanin receptor subtypes namely the GalR1, GalR2 and GalR3, which have only been identified in mammals. In contrast to the extensive studies in mammals, little is known about the structures and functions of galanin and its receptors in avian species. In the present study, a total of nine chicken cDNAs including four galanin prepropeptide transcript variants (cGal -v1 to -v4), the three known galanin receptor subtypes (cGalR1, cGalR2 and cGalR3), and two novel galanin receptor subtypes designated the GalR1-like (cGalR1-L) and GalR2-like (cGalR2-L), were cloned from the brain and intestine tissues, respectively. The four cGal transcript variants encode precursor peptides of 117, 141, 88 and 150 residues, respectively, which eventually produce two isoforms of mature chicken galanin peptide, the cGal (1-29) and a novel cGal (1-53), through proteolytic processing of the galanin prepropeptide. The five isolated cGalR cDNAs encode receptor proteins of 357-to 405-residue-long, which share amino acid sequence identities ranged from 50% to 86% with their corresponding mammalian counterparts. From RT-PCR analysis, the cGal and cGalRs (except for cGalR3) showed diverse mRNA expression profiles among the adult chicken tissues examined including different regions of the oviduct. Using luciferase reporter systems, it was demonstrated that all the five cGalRs, transiently transfected in Chinese hamster ovary (CHO) cells, were functionally and differentially coupled to Gs, Gi or Gq protein signalling pathways upon the activations of chicken galanin peptides cGal (1-29), cGal (1-53) and human galanin-like peptide hGALP (1-60), with distinct potencies. The newly identified cGalR1-L and cGalR2-L share similarities with cGalR1 and cGalR2, respectively, in terms of the sequence homology, exon/intron organization and signalling pathways, thus suggesting an early gene duplication event in vertebrate evolution in the galanin receptor family. On the other hand, the failure of identifying GalR1-L and GalR2-L genes in mammalian species suggests their deletion events in the mammalian lineage, which are supported by the comparative synteny analyses of galanin receptor family between the human, chicken, zebrafish and Xenopus genomes. Together, these findings establish a molecular basis to elucidate the physiological roles of galanin and its receptors in birds.
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Biological Sciences
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Master of Philosophy
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23

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.

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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.
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24

De, Joydeep. "Les signaux quotidiens et saisonniers modulent la configuration du réseau neuronal d'horloge circadienne". Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLS256.

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L'omniprésence des horloges circadiennes à travers une vaste gamme de taxons démontre la valeur adaptative de connaître l'heure du jour. Ces horloges permettent aux organismes de synchroniser leurs processus biologiques quotidiens à des environnements externes et internes changeants. Dans mon projet de doctorat, j'ai utilisé la drosophile comme système modèle pour étudier les bases neurales de l'adaptation saisonnière de l'activité quotidienne par l'horloge. Chez la drosophile, l'horloge cérébrale régulant l'activité locomotrice, suivant un modèle bimodale, fonctionne comme un réseau multi-oscillateurs. Deux ensembles distincts de neurones contrôlent l'activité du matin et l’activité du soir quotidiennement. Les neurones contribuant à l'activité du soir sont nombreux (oscillateurs E : 6 LNds, 1 sLNv et environ 12 à 15 DN1ps dans chaque hémisphère) et très divers en termes de localisations anatomiques, de motifs de projection, de neurochimie et de modalités photoréceptives. Mon travail indique que les différents oscillateurs E possèdent également des activités fonctionnelles distinctes dans le réseau neuronal d'horloge. J’ai démontré que seulement 2 paires d'oscillateurs E (ITP + CRY +) sur environ 150 neurones d'horloge sont suffisantes pour l'activité d'anticipation du soir. La dissection génétique de divers sous-ensembles d'oscillateurs du soir indique que non seulement ces deux paires de neurones sont suffisantes pour l'activité du soir, mais également qu'elles sont fonctionnellement supérieures aux autres oscillateurs du soir. Par conséquent, une hiérarchie opérationnelle existe parmi les oscillateurs du soir dans lesquels les neurones oscillateurs ITP + CRY + (dorénavant, ITP E) occupent l'échelon le plus élevé. J’ai par ailleurs démontré que cette hiérarchie est plutôt flexible, et que les partenaires de cette relation hiérarchique changent de rôle en fonction des entrées neuropeptidergiques (à savoir, le PDF). Les comportement et les réponses calciques des divers neurones du soir suggèrent que le PDF et les signaux saisonniers agissent sur un cadre fonctionnel, dans lequel certains neurones construisent l'activité du soir en augmentant l’activité en fin de journée et que d'autres neurones y contribuent en inhibant l'activité du début d'après-midi. Mise à part le PDF, les indices saisonniers, tels que la durée du jour, l'intensité lumineuse et la température, déterminent la pondération fonctionnelle parmi les oscillateurs du soir. Les signaux saisonniers influencent différents oscillateurs pour remplir la même fonction sous différentes saisons. Les oscillateurs ITP E sont recrutés principalement dans des conditions hivernales, tandis que les oscillateurs non-ITP E contribuent davantage dans des conditions semblables à celles de l'été. Ce recrutement biaisé d'oscillateurs se produit en partie via la modulation des niveaux de PDF par des indices saisonniers.Même s'il existe de nombreux oscillateurs E dans le circuit neuronal circadien, leur pertinence fonctionnelle est définie par des stimuli externes (indices saisonniers) et internes (neuropeptides) grâce au recrutement de différents oscillateurs.En résumé, mon étude de doctorat tente de fournir une explication plausible sur la manière dont l'adaptation saisonnière de l'horloge circadienne est réalisée au niveau neuronal. Mes résultats supportent l'idée que le recrutement d'oscillateurs, contrôlé par l'environnement, facilite l'ajustement saisonnier sculpté par l'horloge circadienne multi-oscillateurs.LNd: dorsal-lateral neuronssLNv: small ventral-lateral neuronsDN1p: dorsal neurons 1 (posterior)ITP: Ion Transport PeptideCRY: CryptochromePDF: Pigment Dispersing Factor
The ubiquity of circadian clocks across a vast range of taxa signifies the adaptive value of knowing the time of the day. These clocks enable organisms to synchronize their daily biological processes to changing external and internal environments. In my PhD project, I used Drosophila as a model system to test hypotheses regarding the neural basis of the seasonal adaptation of the clock-driven daily activity pattern. In Drosophila, the brain clock regulating bimodal locomotor activity functions as a multi-oscillator network. Two distinct sets of neurons control morning and evening bouts of daily locomotor activity. Neurons contributing to the evening activity (E oscillators; 6 LNds, 1 sLNv and around 12 to 15 DN1ps in each hemisphere) are numerous and quite diverse within themselves in terms of their anatomical loci, projection patterns, neurochemistry, and photoreceptive modalities. My work indicates that the different E oscillators also possess distinct functional loci in the clock neuronal network. I show that only 2 pairs of E oscillators (ITP+ CRY+) out of around 150 clock neurons are sufficient for the evening anticipatory activity. Genetic dissection of various evening oscillator subsets further indicates that not only these two pairs of neurons are sufficient for the evening activity, but also, they are functionally superior to other evening oscillators in their contribution to the evening activity. Hence, an operational hierarchy exists among the evening oscillators in which the ITP+ CRY+ (henceforth, ITP E) oscillator neurons inhabit the highest rung. I further show that this hierarchy is rather flexible, and the partners of this hierarchical relationship switch roles depending on neuropeptidergic inputs (namely, PDF). Studying behavior and calcium responses in diverse evening neurons suggest that PDF and seasonal cues act on a functional framework of E neurons in which some build evening activity by promotion of activity in the later parts of the day and while others, by inhibiting activity in the earlier afternoon. Alongside PDF, seasonal cues such as day-length, light intensity and temperature, determine the functional weightage among evening oscillators. Specific seasonal cues recruit different oscillators to carry out the same function under different seasons. ITP E oscillators are recruited mostly by winter-like conditions whereas non- ITP E oscillators contribute more under summer-like conditions. This biased recruitment of oscillators partly occurs via modulation of the PDF levels by seasonal cues. Even though there are numerous E oscillators in the brain circadian circuit, their functional relevance is defined by external (seasonal cues) and internal (neuropeptides) environments through conditional oscillator recruitment. In summary, my PhD study attempts to provide a plausible explanation of how seasonal adaptation of the circadian clock and the behaviours that it times, is achieved at the neural level. My results support the idea that environmentally gated recruitment of oscillators facilitates seasonal adjustment of the daily activity pattern sculpted by the multi-oscillator circadian clock.LNd: dorsal-lateral neuronssLNv: small ventral-lateral neuronsDN1p: dorsal neurons 1 (posterior)ITP: Ion Transport PeptideCRY: CryptochromePDF: Pigment Dispersing Factor
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25

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.

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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.
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26

Moller, Kristian. "Pituitary adenylate cyclase activating peptide (PACAP) an experimental study on the expression and regulation in the peripheral nervous system /". Lund : Dept. of Physiology and Neuroscience, neuroendocrine Cell Biology, Lund University, 1997. http://books.google.com/books?id=Fw5rAAAAMAAJ.

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27

Chaloin, Olivier. "Synthèse d'analogues peptidiques et pseudopeptidiques du neuropeptide Y". Montpellier 2, 1996. http://www.theses.fr/1996MON20100.

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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
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28

Tuzmen, Ceren. "Regulation of Bone Differentiation Through the Neuropeptides". Research Showcase @ CMU, 2017. http://repository.cmu.edu/dissertations/1083.

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This dissertation aims to demonstrate immunoregulatory roles of neuropeptides in bone metabolism both in bone and non-bone microenvironments. Substance P (SP) and calcitonin gene-related peptide (CGRP) are sensory neuropeptides that have been associated with various aspects of the pathophysiology of heterotopic ossification (HO) of soft tissues. These aspects include dysregulation of inflammation, mainly governed by macrophages and mast cells, and bone morphogenetic protein (BMP) signaling. The first set of experiments presented here contributes to the understanding of the involvement of the neuropeptides with HO pathophysiology. Results of these experiments illustrate that the delivery of SP, with no exogenous BMP or direct trauma to the tissue, is sufficient to induce inflammation, upregulate BMP2 expression and HO in murine Achilles tendon, while CGRP delivered together with SP can suppress the inflammatory changes and HO induced by SP. This is the first study that involves direct administration of these neuropeptides into the tendon to investigate their direct effects in the induction of HO. This was enabled by the use of biopatterning technology, which introduced spatial control of the tissue microenvironment by using inkjet-based deposition of the neuropeptides onto collagen scaffolds, i.e. Acellular DermaMatrix (ADM) constructs, and implanting these constructs in vivo. Additionally, in vitro studies demonstrated an interaction between SP and CGRP in direct and indirect regulation of BMP2 signaling. One of the main contributions of the in vitro experiments is that CGRP can counteract the augmenting effects of SP on BMP2 signaling and therefore down-regulate BMP2-induced bone differentiation when combined with SP. Moreover, SP, despite its inflammatory potential, can suppress the inhibitory effects of the inflammatory response that is mediated by macrophage activation on BMP2 signaling, and this effect can be mitigated by CGRP. Therefore, this finding provides additional evidence for the contribution of macrophages together with neuropeptide-mediated inflammation to the induction of HO. The final set of experiments explored the use of vasoactive intestinal peptide (VIP) as a therapeutic approach to improve BMP2-induced bone haling during inflammatory conditions. In order to investigate this problem, a critical-defect model was used, where ADM biopattened with bacterial lipopolysaccharide (LPS), to induce inflammation, VIP and BMP2 were delivered into mouse calvaria to induce bone healing in the presence of inflammation. LPS was shown earlier to have inhibitory effects on BMP2-induced bone healing by creating an inflammatory microenvironment. Our findings indicate that VIP can mitigate inhibitory effects of LPS on BMP2-induced bone differentiation in vitro and bone healing in vivo. Overall, the work presented here adds to the understanding of the interaction between the peripheral nervous system and bone metabolism through regulation of the immune responses in musculoskeletal pathologies.
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29

Aromataris, Edoardo Claudio. "Opioid neuropeptides in the guinea-pig heart /". Title page and summary only, 1994. http://web4.library.adelaide.edu.au/theses/09SB/09sba769.pdf.

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30

Wozniak, Andrzej. "The role of neuropeptides in inflammatory disease /". Title page, contents and summary only, 1992. http://web4.library.adelaide.edu.au/theses/09PH/09phw938.pdf.

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Thesis (Ph. D.)--University of Adelaide, Dept. of Medicine, 1993.
Copies of author's previously published articles inserted. Amendments (2 leaves) in front cover pocket. Includes bibliographical references (leaves 227-259).
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31

Abusnana, Salahedeen Emhemed Elmansuri. "Hypothalamic neuropeptides in regulation of feeding behaviour". Thesis, Imperial College London, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.391263.

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32

Jenkins, D. W. "Prostaglandins and neuropeptides in rat trigeminal neurones". Thesis, University of Cambridge, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.605089.

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Having identified prostaglandin receptors in trigeminal tissue, the functional effects of prostaglandin receptor ligands on CGRP release were investigated using cultured adult rat trigeminal ganglion neurones as a model system. It was found that calcium-dependent CGRP release could be stimulated following stimulation of DP, EP and IP receptors. Furthermore, the use of EP receptor specific agonists and antagonists suggested that the EP receptor subtype involved might be the EP2 receptor. The effects of several agents on prostaglandin E2 (PGE2) release from the cultured rat trigeminal neurones were also evaluated. From these data it was concluded that PGE2 itself could be released in a p42/p44 MAP kinase and protein kinase C-dependent manner following treatment with the algesic peptide, bradykinin, but not after depolarisation or treatment with either capsaicin or CGRP. Finally, superfusion studies were conducted to measure CGRP release from TNC slices in vitro. In this experimental model it was found that calcium-dependent CGRP release was stimulated by depolarisation and capsaicin treatment. Furthermore, evidence was obtained to suggest that although exogenous prostaglandins did not cause CGRP release per se in this system, they were able to modulate chemically stimulated CGRP release. In summary, this study has shown: (1) the presence of EP and IP prostanoid receptors in rat trigeminal ganglia, (2) that CGRP is released from cultured trigeminal neurones following DP, EP and IP receptor activation, (3) that PGE2 is released by bradykinin from the same neuronal cultures and (4) that CGRP release from TNC neurones is also prostaglandin-sensitive. Taken together, these data provide further evidence for important roles of both prostaglandins and CGRP in the pathophysiology of migraine headache.
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33

Eedy, David John. "Neuropeptides in skin in health and disease". Thesis, Queen's University Belfast, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.335268.

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34

Moffett, C. L. "Structural and functional characterization of nematode neuropeptides". Thesis, Queen's University Belfast, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.390877.

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35

Hooper, Nigel Mark. "Metabolism of neuropeptides by cell-surface peptidases". Thesis, University of Leeds, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.235486.

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36

Khan, Mohamed Michael Tariq. "Neuropeptides and cytokines in regenerating peripheral nerve". Thesis, University College London (University of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.243451.

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37

Rowe, Matthew Lyndon. "Structure and function of sea urchin neuropeptides". Thesis, Queen Mary, University of London, 2010. http://qmro.qmul.ac.uk/xmlui/handle/123456789/599.

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The subject of this thesis is the identification and functional characterization of sea urchin neuropeptides. Neuropeptides are important mediators of neural signalling in all known animals with a nervous system, including bilaterians, ctenophorans, and cnidarians. Sea urchin neuropeptides are of particular interest for three significant reasons; echinoderms have a radically different secondarily-derived pentaradial body structure, sea urchins have served as model organisms for research into embryonic development, and thirdly because the genome of a sea urchin, the purple sea urchin Strongylocentrotus purpuratus (Stimpson, 1857) has been sequenced (Sodergren et al., 2006). Only one family of neuropeptides, the SALMFamides, has previously been characterized in all classes of the phylum Echinodermata. The thesis reports the identification of putative neuropeptide GPCRs and at least seven novel sea urchin neuropeptide genes using genomic and Expressed Sequence Tag (EST) analysis. The novel sea urchin neuropeptides identified include putative homologues of vasotocin, the sea cucumber neuropeptide NGIWYamide, thyrotropin-releasing hormone, gonadotropin-releasing hormone, and calcitonin. A further three peptide precursor genes encoding peptides lacking strong homology to any known peptides were also identified and the peptides have been named GKamides and Pedal Peptide-like Neuropeptides. Two of the peptide precursor genes, those encoding peptides homologous to vasotocin and NGIWYamide, also each encode neurophysin domains, which have previously only been identified in association with vasopressin/oxytocin-like peptides. Biochemical and pharmacological techniques were employed to investigate the occurrence and functions of the putative neuropeptides identified. These included mass spectroscopy and in vitro bioassays, the former to detect the putative novel neuropeptides identified in this study and the latter to investigate bioactivity of the peptides in sea urchins. The thesis provides evidence of the neural expression and bioactivity of novel sea urchin neuropeptides and contributes to our understanding of the role of neuropeptides in echinoderm physiology and behaviour.
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38

Jones, Christine Ann. "Monoclonal antibodies in the study of neuropeptides". Thesis, Imperial College London, 1991. http://hdl.handle.net/10044/1/46848.

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39

Augé, Sophie. "Topographie intramembranaire de neuropeptides : quelques approches membranaires". Toulouse 3, 1996. http://www.theses.fr/1996TOU30125.

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La conformation membranaire d'un neuropeptide peut etre determinee par la technique rmn de l'effet overhauser nucleaire transfere (trnoe), a partir du peptide en interaction avec des liposomes constitues de phospholipides perdeuteries. Une souche de levure methylotrophe, pichia angusta, a ete adaptee a la croissance en milieu perdeuterie. Ceci a permis d'isoler des phospholipides (130 mg), des glycolipides et de l'ergosterol (30 mg) perdeuteries a 97,5%, a partir d'une culture en fermenteur de 1,5 l (24 gde matiere seche). L'etude de la neurokinine a (nka) par trnoe a ete entreprise apres l'attribution des deplacements chimiques. La nka n'interagit pas avec des liposomes neutres. Par contre, l'interaction entre le peptide et des liposomes charges negativement (phosphatidylglycerol (pg) entre 0,1% et 30% molaire) se traduit par un elargissement des raies du spectre rmn et une precipitation du complexe peptides-lipides. Cette interaction s'est averee etre trop forte pour observer des trnoe, ceci meme en presence de liposomes contenant 0,1% de pg. L'orientation de la substance p (sp) par rapport a la membrane a ete determinee par rmn solide de l'azote-15. La sp a ete marquee au #1#5n sur la phe#7 et la phe#8. Apres mise au point d'un nouveau protocole d'obtention de bicouches lipidiques orientees (caracterisees par la rmn-#2h et la rmn-#3#1p), les deplacements chimiques #1#5n ont ete mesures et montrent que la sp n'est pas structuree en helice inseree perpendiculairement au plan de la membrane. Une technique rmn a ete developpee afin de localiser un peptide dans une membrane. Elle repose sur l'observation de trnoe heteronucleaires intermoleculaires, entre le fluor du 6-fluoro-cholesterol et les protons du peptide. Les resultats preliminaires montrent la faisabilite de cette approche qui necessite cependant d'utiliser du 6-fluoro cholesterol deuterie au voisinage du fluor afin de limiter la diffusion de spins
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40

Smith, Gary D. "Steroid regulation of neuropeptides in sensory neurons". Thesis, University of Edinburgh, 1992. http://hdl.handle.net/1842/20198.

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Primary afferent neurons with perikarya in the dorsal root ganglia (drg) mediate the transmission of sensory information from the periphery and viscera to the spinal cord. A number of neuropeptides, including substance P (SP), somatostatin (SS) and calcitonin gene related peptide (CGRP) have been localised in discrete but often overlapping subpopulations of drg neurons. These neuropeptides have been implicated in nociception and neurogenic inflammation, both processes which can be influenced by steroid hormones. Whilst steroid hormones have been shown to regulate synthesis of a number of neuropeptides including SP, SS and CGRP in the central nervous system, it is not known if they influence neuropeptides in the drg. In this thesis I have investigated the regulation of SP, SS and CGRP by steroids in vivo and in dissociated primary cultures of adult drg neurons. The SP, SS and CGRP content of drg from C1 to L6 was determined and a differential distribution of the three neuropeptides was found. Drg wet weight and SP content were greatest in drg from the cervical (C6 - T1) and lumbar (L4 - L6) enlargements. CGRP content tended to be greater in drg from more caudal areas (T10 - L6) and SS content was uniform in most drg but was notably lower in drg from area C5 - C7. The regulation of neuropeptides in the drg by two classes of steroid, adrenal steroids and androgens, was investigated. Adrenalectomy (ADX) of adult male Wistar rats increased SP and CGRP and decreased SS content of cervical drg. The effects of ADX were reversed by subcutaneous implantation of pellets containing corticosterone (B) or by daily subcutaneous injection of dexamethasone (DEX). The neuropeptide content of drg was not regulated by androgens; no significant change in the SP, SS or CGRP contents of drg were found following castration or administration of supraphysiological testosterone.
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41

Jinsmaa, Yunden. "Designing of Novel Neuropeptides Improving Learning Performance". Kyoto University, 1999. http://hdl.handle.net/2433/181886.

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Kyoto University (京都大学)
0048
新制・課程博士
博士(農学)
甲第7877号
農博第1035号
新制||農||776(附属図書館)
学位論文||H11||N3240(農学部図書室)
UT51-99-G471
京都大学大学院農学研究科食品工学専攻
(主査)教授 佐々木 隆造, 教授 吉川 正明, 教授 伏木 亨
学位規則第4条第1項該当
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42

Kadri-Guissi, Sanae. "Expression de gènes spécifiant des précurseurs de neuropeptides, chez un ver marin, Nereis diversicolor". Lille 1, 1989. http://www.theses.fr/1989LIL10060.

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Caractérisation des précurseurs de la cholecystokinine, de la dymorphine 1-17 et de l'-neo-endorphine par traduction in vitro et in ovo des ARN messagers isolés du cerveau de n-diversicolor et à l'aide d'anticorps spécifiques
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43

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/.

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44

Tousignant, Christine. "Effets des neuropeptides sur le système nerveux autonome". Mémoire, Université de Sherbrooke, 1987. http://hdl.handle.net/11143/11703.

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Les neurokinines et les kinines sont de puissants stimulants des vas deferens de rat, de lapin et de cobaye : elles augmentent l'effet de la stimulation électrique de base en facilitant la libération du ou des neurotransmetteur(s) qui activent les récepteurs musculaires. Les sites réceptoriels pré et postsynaptiques ont été étudiés séparément dans les vas deferens alors que cette distinction n'a pas été possible pour l'artère pulmonaire de lapin stimulée. La partie prostatique des vas deferens a été utilisée pour étudier le ou les sites préjonctionels alors que la partie épididymale s'est révélée adéquate pour l'étude du ou des sites postjonctionels. Les récepteurs pré et postsynaptiques des neurokinines, caractérisés par l'ordre de puissance des agonistes, semblent être de type NK-A dans le vas deferens de rat, de lapin et dans l'artère pulmonaire de lapin stimulée alors que le vas deferens de cobaye aurait des récepteurs de type NK-P. Les neurokinines sont inactives dans la partie épididymale du vas deferens de cobaye. Les récepteurs des kinines sont aussi présents au niveau des 2 sites fonctionnels dans les vas deferens de rat, de lapin et de cobaye et ils sont identiques. Ces récepteurs sont de type B2 sur le vas deferens de rat et de lapin. L'artère pulmonaire de lapin stimulée semble être un système à récepteur unique de type B1 alors que le vas deferens de lapin semble être un système à deux récepteurs constitué des récepteurs B1 et B2. Les critères retenus pour classifier les récepteurs des kinines dans les vas deferens et dans l'artère pulmonaire sont l'ordre de puissance des agonistes et l'affinité d'antagonistes tel la [Thi5,8, D-Phe7]-BK. Cependant ce compose a montré un effet agoniste sur la partie prostatique du vas deferens de rat, une préparation de type B2. La [D-Arg0, Hyp3, Thi5,8, D-Phe7]-BK, un antagoniste des récepteurs B2 n'a montré aucun effet agoniste sur la partie prostatique du vas deferens de rat. L'étude effectuée sur les vas deferens avec les peptides opiacés a démontré la présence des récepteurs sigma et mu dans le vas deferens de rat et du récepteur kappa dans le vas deferens de lapin. Le vas deferens de cobaye est peu sensible aux peptides opiacés de type mu, kappa et sigma. D'autres peptides testés sont des excitateurs ou des inhibiteurs de la stimulation électrique des vas deferens. Leurs récepteurs n'ont pu être caractérisés puisque les agonistes et les antagonistes de ces composés n'étaient pas disponibles pour cette étude.
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45

Moheimen, Jamil. "Striatal neuropeptides associated with L- DOPA-induced dyskinesia". Thesis, Uppsala universitet, Institutionen för farmaceutisk biovetenskap, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-209915.

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Abstract Striatal neuropeptides associated with L-DOPA-induced dyskinesia 2012-02-14 Parkinson's disease (PD) is the most common neurodegenerative disease, with approximately 6 million sufferers in the world. The patients are usually diagnosed between the ages 50-70 years and as the disease progress more symptoms may occur. The cause of the disease is unknown, but the characteristic of PD is that it is a selective degeneration of dopaminergic neurons in the substantia nigra, which leads to an absence of dopamine release in striatum. This affects the motor system of the central nervous system, resulting in a movement disorder. It is not until 70% of the dopamine neurons have been lost that the patient will show the first symptoms of the disease. This will thereby complicate the treatment of the disease. When the motor symptoms are established, it is extremely difficult to stop or reverse the disease. The most effective treatment of patients with Parkinson's disease is L-DOPA that is converted to dopamine in the brain. Dopamine agonists have also been used as a treatment alternative in PD in attempts to avoid the motor symptoms. However, everyone who gets Parkinson's disease will eventually be required to start using L-DOPA as the disease worsen and dopamine agonists loses in efficacy. The majority of patients being treated with L- DOPA have disturbing adverse reactions during the treatment as involuntary, abnormal movements, known as dyskinesias may develop. Once you have got dyskinesias it will not disappear and cannot be effectively alleviated, and will therefore often impair the person's daily life. It is therefore a major focus in research to find new treatments focused on L-DOPA induced side-effects. In a previous study several unknown neuropeptides has been detected, which might have a strong correlation between the L-DOPA and dyskinesia. The main purpose of this study is to identify these neuropeptides and locate them in the striatum of high and low dyskinetic rats. This was performed by using MALDI imaging mass spectrometry and the computer program FlexImaging that provides a visualization of peptides and proteins and their distribution in tissue sections. Of the 76 peptide families that were found in rat brains, 33 of them were identified in this study, and some of them proved to be of high interest. From these 33, three neuropeptides; corticoliberin, P3(42) and cholecystokinin-39, were chosen for further investigation. We saw elevated levels of these three in both high and low dyskinetic rats. We were able to verify with antibodies their localization in normal brains in the striatum and hippocampus. In the future, these peptides will be studied in dyskinetic rats to verify if they are significantly elevated in dyskinetic animals. These three peptides together with the other identified peptides are very interesting in hopes to be able to cure or ameliorate L- DOPA-induced dyskinesias.
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