Статті в журналах: "GALR2"

1

Kiezun, Jacek, Janusz Godlewski, Bartlomiej E. Krazinski, Zygmunt Kozielec, and Zbigniew Kmiec. "Galanin Receptors (GalR1, GalR2, and GalR3) Expression in Colorectal Cancer Tissue and Correlations to the Overall Survival and Poor Prognosis of CRC Patients." International Journal of Molecular Sciences 23, no. 7 (March 29, 2022): 3735. http://dx.doi.org/10.3390/ijms23073735.

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Colorectal cancer (CRC) is the second most common cause of cancer in women and the third in men. The postoperative pathomorphological evaluation of patients with CRC is extremely important for future therapeutic decisions. Although our previous studies demonstrated high galanin (GAL) presence within tumor tissue and an elevated concentration of GAL in the serum of CRC patients, to date, there is a lack of data regarding GAL receptor (GalR) protein expression in CRC cells. Therefore, the aim of this study was to evaluate the presence of all three types of GalRs (GalR1, GalR2 and GalR3) within epithelial cells of the human colon and CRC tissue with the use of the immunohistochemical method and to correlate the results with the clinical-pathological data. We found stronger immunoreactivity of GalR1 and GalR3 in CRC cells compared to epithelial cells of the unchanged mucosa of the large intestine. No differences in the GalR2 protein immunoreactivity between the studied tissues were noted. We also found that the increased immunoexpression of the GalR3 in CRC tissue correlated with the better prognosis and longer survival (p < 0.0079) of CRC patients (n = 55). The obtained results suggest that GalR3 may play the role of a prognostic factor for CRC patients. Based on data from the TCGA-COAD project deposited in the GDC Data Portal, we also found that GalR mRNA in cancer samples and the adjacent normal tissue did not correlate with immunoexpression of the GalR proteins in CRC cells and epithelial cells of the unchanged mucosa.

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2

Kramáriková, I., J. Šípková, P. Šída, S. Hynie, and Věra Klenerová. "The Effect of Stress on the Galaninergic System in the Rat Adenohypophysis: mRNA Expression and Immunohistochemistry of Galanin Receptors." Folia Biologica 63, no. 5-6 (2017): 197–201. http://dx.doi.org/10.14712/fb2017063050197.

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The neuropeptide galanin is a widely distributed neurotransmitter/neuromodulator that regulates a variety of physiological processes and also participates in the regulation of stress responses. The effect of stress is dependent on the activity of the hypothalamic- adenohypophyseal-adrenal axis. Although the adenohypophysis is a crucial part of this axis, galanin peptides and their receptors have not yet been identified in this part of the pituitary after activation of the stress response. Since there are many controversies about the occurrence of individual galanin receptor subtypes in the adenohypophysis under basal conditions, we decided to verify their presence immunohistochemically, and we clearly demonstrated that the adenohypophysis expresses neuropeptides galanin, galanin-like peptide, and subtypes of galanin receptors GalR1, GalR2 and GalR3. The specificity of the reactions was confirmed by Western blots for galanin receptors. Using real-time qPCR we also demonstrated the presence of three GalR subtypes, with the highest expression of GalR2. In addition, we tested the effect of stress. We found that acute stress did not induce any changes in the GalR2 expression, but increased expression of GalR1 and decreased that of GalR3. We confirmed the involvement of the galanin system in the stress regulation in the adenohypophysis.

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3

Gottsch, Michelle L., Hongkui Zeng, John G. Hohmann, David Weinshenker, Donald K. Clifton, and Robert A. Steiner. "Phenotypic Analysis of Mice Deficient in the Type 2 Galanin Receptor (GALR2)." Molecular and Cellular Biology 25, no. 11 (June 1, 2005): 4804–11. http://dx.doi.org/10.1128/mcb.25.11.4804-4811.2005.

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ABSTRACT Galanin is a neuropeptide implicated in the regulation of feeding, reproduction, cognition, nociception, and seizure susceptibility. There are three known galanin receptor (GALR) subtypes (GALR1, GALR2, and GALR3), which bind to galanin with different affinities and have their own unique distributions, signaling mechanisms, and putative functions in the brain and peripheral nervous system. To gain further insight into the possible physiological significance of GALR2, we created mutant mice that were deficient in GALR2 and compared their phenotype to that of wild-type (WT) littermate or age-matched controls, with respect to basic motor and sensory function, feeding behavior, reproduction, mood, learning and memory, and seizure susceptibility. Phenotypic analysis revealed that animals bearing a deletion of GALR2 did not differ significantly from their WT controls in any of the measured variables. We conclude that either GALR2 plays no role in these physiological functions or through redundancy or compensation these mutant animals can adapt to the congenital absence of GALR2. It is also conceivable that GALR2 plays only a subtle role in some of these functions and that the impact of its loss could not be detected by the analytical procedures used here.

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4

Kim, Dong-Kyu, Seongsik Yun, Gi Hoon Son, Jong-Ik Hwang, Cho Rong Park, Jae Il Kim, Kyungjin Kim, Hubert Vaudry, and Jae Young Seong. "Coevolution of the Spexin/Galanin/Kisspeptin Family: Spexin Activates Galanin Receptor Type II and III." Endocrinology 155, no. 5 (May 1, 2014): 1864–73. http://dx.doi.org/10.1210/en.2013-2106.

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The novel neuropeptide spexin (SPX) was discovered using bioinformatics. The function of this peptide is currently under investigation. Here, we identified SPX along with a second SPX gene (SPX2) in vertebrate genomes. Syntenic analysis and relocating SPXs and their neighbor genes on reconstructed vertebrate ancestral chromosomes revealed that SPXs reside in the near vicinity of the kisspeptin (KISS) and galanin (GAL) family genes on the chromosomes. Alignment of mature peptide sequences showed some extent of sequence similarity among the 3 peptide groups. Gene structure analysis indicated that SPX is more closely related to GAL than KISS. These results suggest that the SPX, GAL, and KISS genes arose through local duplications before 2 rounds (2R) of whole-genome duplication. Receptors of KISS and GAL (GAL receptor [GALR]) are phylogenetically closest among rhodopsin-like G protein-coupled receptors, and synteny revealed the presence of 3 distinct receptor families KISS receptor, GALR1, and GALR2/3 before 2R. A ligand-receptor interaction study showed that SPXs activate human, Xenopus, and zebrafish GALR2/3 family receptors but not GALR1, suggesting that SPXs are natural ligands for GALR2/3. Particularly, SPXs exhibited much higher potency toward GALR3 than GAL. Together, these results identify the coevolution of SPX/GAL/KISS ligand genes with their receptor genes. This study demonstrates the advantage of evolutionary genomics to explore the evolutionary relationship of a peptide gene family that arose before 2R by local duplications.

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5

Jana, Barbara, Jarosław Całka, and Bartosz Miciński. "Regulatory Influence of Galanin and GALR1/GALR2 Receptors on Inflamed Uterus Contractility in Pigs." International Journal of Molecular Sciences 22, no. 12 (June 15, 2021): 6415. http://dx.doi.org/10.3390/ijms22126415.

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Uterine inflammation is a very common and serious pathology in domestic animals, the development and progression of which often result from disturbed myometrial contractility. We investigated the effect of inflammation on the protein expression of galanin (GAL) receptor subtypes (GALR)1 and GALR2 in myometrium and their role in the contractile amplitude and frequency of an inflamed gilt uterus. The gilts of the E. coli and SAL groups received E. coli suspension or saline in their uteri, respectively, and only laparotomy was performed (CON group). Eight days later, the E. coli group developed severe acute endometritis and lowered GALR1 protein expression in the myometrium. Compared to the pretreatment period, GAL (10−7 M) reduced the amplitude and frequency in myometrium and endometrium/myometrium of the CON and SAL groups, the amplitude in both stripes and frequency in endometrium/myometrium of the E. coli group. In this group, myometrial frequency after using GAL increased, and it was higher than in other groups. GALR2 antagonist diminished the decrease in amplitude in myometrium and the frequency in endometrium/myometrium (SAL, E. coli groups) induced by GAL (10−7 M). GALR1/GALR2 antagonist and GAL (10−7 M) reversed the decrease in amplitude and diminished the decrease in frequency in both examined stripes (CON, SAL groups), and diminished the drop in amplitude and abolished the rise in the frequency in the myometrium (E. coli group). In summary, the inflammation reduced GALR1 protein expression in pig myometrium, and GALR1 and GALR2 participated in the contractile regulation of an inflamed uterus.

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6

Sun, Jing, Shu Xu, Hui Li, Liang Li, and Zhi-Qing David Xu. "Galanin Protects Rat Cortical Astrocyte from Oxidative Stress: Involvement of GalR2 and pERK1/2 Signal Pathway." Mediators of Inflammation 2019 (May 22, 2019): 1–9. http://dx.doi.org/10.1155/2019/2716028.

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The neuropeptide galanin and its receptors have been found to have protective effects on neurons. However, the role of galanin on astrocytes is still unclear. The present study is aimed at investigating the effects of galanin on the viability of cultured rat cortical astrocytes after oxidative stress induced by H2O2 and possible receptor and signaling mechanisms involved. Treatment of galanin had significant protective effects against H2O2-induced toxicity in the cultured cortical astrocytes. H2O2 induced an upregulation of phosphorylated extracellular signal-related kinase1/2 (pERK1/2) in astrocytes, which was suppressed by coapplication of galanin, suggesting an involvement of the pERK1/2 signal pathway in the protective effects of galanin. GalR2 has higher expression levels than GalR1 and GalR3 in the cultured cortical astrocytes, and GalR2 agonist AR-M1896 mimicked galanin effects on the astrocytes, implying that galanin protective effects mainly mediated by GalR2. Meanwhile, galanin had no effect on the A1-type transformation of rat cortical astrocytes. All those results suggest that galanin protects rat cortical astrocytes from oxidative stress by suppressing H2O2-induced upregulation of pERK1/2, mainly through GalR2.

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7

Berger, Alexandra, Roland Lang, Kerstin Moritz, Radmila Santic, Anton Hermann, Wolfgang Sperl, and Barbara Kofler. "Galanin Receptor Subtype GalR2 Mediates Apoptosis in SH-SY5Y Neuroblastoma Cells." Endocrinology 145, no. 2 (February 1, 2004): 500–507. http://dx.doi.org/10.1210/en.2003-0649.

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Abstract Recently we have shown that galanin binding significantly correlates with survival in neuroblastoma patients, indicating a possible modulatory role of galanin receptors in neuroblastic tumor biology. However, the molecular mechanisms beyond this correlation have not been elucidated. Here, the cellular effects on activation of specific galanin receptor subtypes in human SH-SY5Y neuroblastoma cells were analyzed using a tetracycline-controlled expression system. Pharmacological studies confirmed the inducible expression of high affinity binding sites for galanin in SH-SY5Y cells transfected with the galanin receptors GalR1 (SY5Y/GalR1) and GalR2 (SY5Y/GalR2). Microphysiometry revealed that both receptor subtypes were able to mediate an intracellular signal upon galanin application. Interestingly, induction of receptor expression and treatment with 100 nm galanin resulted in a dramatic decrease in cell viability in SY5Y/GalR2 cells (93 ± 3%) compared with a less pronounced effect in SY5Y/GalR1 cells (19 ± 10%). The antiproliferative potency of galanin was 100-fold higher in SY5Y/GalR2 (50% effective concentration, 1.1 nm) than in SY5Y/GalR1 cells (50% effective concentration, 190 nm). Furthermore, activation of receptor expression and exposure to galanin resulted in apparent morphological changes indicative of apoptosis in SY5Y/GalR2 cells only. Induction of cell death by the apoptotic process was confirmed by poly-(ADP-ribose)-polymerase cleavage, caspase-3 activation, and the typical laddering of DNA. This study indicates that a high level of GalR2 expression is able to inhibit cell proliferation and induce apoptosis in neuroblastoma cells and therefore identifies GalR2 as a possible target for pharmacological intervention in neuroblastoma.

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8

Kiezun, Jacek, Marta Kiezun, Bartlomiej Emil Krazinski, Lukasz Paukszto, Anna Koprowicz-Wielguszewska, Zbigniew Kmiec, and Janusz Godlewski. "Galanin Receptors (GALR1, GALR2, and GALR3) Immunoexpression in Enteric Plexuses of Colorectal Cancer Patients: Correlation with the Clinico-Pathological Parameters." Biomolecules 12, no. 12 (November 27, 2022): 1769. http://dx.doi.org/10.3390/biom12121769.

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Galanin (GAL) is an important neurotransmitter released by the enteric nervous system (ENS) neurons located in the muscularis externa and submucosa enteric plexuses that acts by binding to GAL receptors 1, 2 and 3 (GALR1, 2 and 3). In our previous studies, the GAL immunoexpression was compared in colorectal cancer (CRC) tissue and the adjacent parts of the large intestine wall including myenteric and submucosal plexuses. Recently we have also found that expression levels of GALR1 and GALR3 proteins are elevated in CRC tissue as compared with their expression in epithelial cells of unchanged mucosa. Moreover, higher GALR3 immunoreactivity in CRC cells correlated with better prognosis of CRC patients. To understand the distribution of GALRs in enteric plexuses distal and close to CRC invasion, in the present study we decided to evaluate GALRs expression within the myenteric and submucosal plexuses located proximally and distally to the cancer invasion and correlated the GALRs expression levels with the clinico-pathological data of CRC patients. The immunohistochemical and immunofluorescent methods showed only slightly decreased immunoexpression of GALR1 and GALR3 in myenteric plexuses close to cancer but did not reveal any correlation in the immunoexpression of all three GAL receptors in myenteric plexuses and tumour progression. No significant changes were found between the expression levels of GALRs in submucosal plexuses distal and close to the tumour. However, elevated GALR1 expression in submucosal plexuses in vicinity of CRC correlated with poor prognosis, higher tumour grading and shorter overall survival. When myenteric plexuses undergo morphological and functional alterations characteristic for atrophy, GALRs maintain or only slightly decrease their expression status. In contrast, the correlation between high expression of GALR1 in the submucosal plexuses and overall survival of CRC patients suggest that GAL and GALRs can act as a components of local neuro-paracrine pro-proliferative pathways accelerating the invasion and metastasis of cancer cell. The obtained results suggest an important role of GALR1 in submucosal plexuses function during the progression of CRC and imply that GALR1 expression in submucosal plexuses of ENS could be an important predictive factor for CRC progression.

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9

Leciejewska, Natalia, Ewa Pruszyńska-Oszmałek, Karolina Mielnik, Maciej Głowacki, Tomasz P. Lehmann, Maciej Sassek, Bartosz Gawęda, Dawid Szczepankiewicz, Krzysztof W. Nowak, and Paweł A. Kołodziejski. "Spexin Promotes the Proliferation and Differentiation of C2C12 Cells In Vitro—The Effect of Exercise on SPX and SPX Receptor Expression in Skeletal Muscle In Vivo." Genes 13, no. 1 (December 28, 2021): 81. http://dx.doi.org/10.3390/genes13010081.

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SPX (spexin) and its receptors GalR2 and GalR3 (galanin receptor subtype 2 and galanin receptor subtype 3) play an important role in the regulation of lipid and carbohydrate metabolism in human and animal fat tissue. However, little is still known about the role of this peptide in the metabolism of muscle. The aim of this study was to determine the impact of SPX on the metabolism, proliferation and differentiation of the skeletal muscle cell line C2C12. Moreover, we determined the effect of exercise on the SPX transduction pathway in mice skeletal muscle. We found that increased SPX, acting via GalR2 and GalR3 receptors, and ERK1/2 phosphorylation stimulated the proliferation of C2C12 cells (p < 0.01). We also noted that SPX stimulated the differentiation of C2C12 by increasing mRNA and protein levels of differentiation markers Myh, myogenin and MyoD (p < 0.01). SPX consequently promoted myoblast fusion into the myotubule (p < 0.01). Moreover, we found that, in the first stage (after 2 days) of myocyte differentiation, GalR2 and GalR3 were involved, whereas in the last stage (day six), the effect of SPX was mediated by the GalR3 isoform. We also noted that exercise stimulated SPX and GalR2 expression in mice skeletal muscle as well as an increase in SPX concentration in blood serum. These new insights may contribute to a better understanding of the role of SPX in the metabolism of skeletal muscle.

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10

Zalecki, Michal, Judyta Juranek, Zenon Pidsudko, Marzena Mogielnicka-Brzozowska, Jerzy Kaleczyc, and Amelia Franke-Radowiecka. "Inferior vagal ganglion galaninergic response to gastric ulcers." PLOS ONE 15, no. 11 (November 23, 2020): e0242746. http://dx.doi.org/10.1371/journal.pone.0242746.

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Galanin is a neuropeptide widely expressed in central and peripheral nerves and is known to be engaged in neuronal responses to pathological changes. Stomach ulcerations are one of the most common gastrointestinal disorders. Impaired stomach function in peptic ulcer disease suggests changes in autonomic nerve reflexes controlled by the inferior vagal ganglion, resulting in stomach dysfunction. In this paper, changes in the galaninergic response of inferior vagal neurons to gastric ulceration in a pig model of the disease were analyzed based on the authors’ previous studies. The study was performed on 24 animals (12 control and 12 experimental). Gastric ulcers were induced by submucosal injections of 40% acetic acid solution into stomach submucosa and bilateral inferior vagal ganglia were collected one week afterwards. The number of galanin-immunoreactive perikarya in each ganglion was counted to determine fold-changes between both groups of animals and Q-PCR was applied to verify the changes in relative expression level of mRNA encoding both galanin and its receptor subtypes: GalR1, GalR2, GalR3. The results revealed a 2.72-fold increase in the number of galanin-immunoreactive perikarya compared with the controls. Q-PCR revealed that all studied genes were expressed in examined ganglia in both groups of animals. Statistical analysis revealed a 4.63-fold increase in galanin and a 1.45-fold increase in GalR3 mRNA as compared with the controls. No differences were observed between the groups for GalR1 or GalR2. The current study confirmed changes in the galaninergic inferior vagal ganglion response to stomach ulcerations and demonstrated, for the first time, the expression of mRNA encoding all galanin receptor subtypes in the porcine inferior vagal ganglia.

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11

Oliveira Volpe, Caroline Maria, Tatiana Vaz, Fabiana Rocha-Silva, Pedro Henrique Villar-Delfino, and José Augusto Nogueira-Machado. "Is Galanin a Promising Therapeutic Resource for Neural and Nonneural Diseases?" Current Drug Targets 21, no. 9 (July 28, 2020): 922–29. http://dx.doi.org/10.2174/1389450121666200225112055.

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Background: Galanin (GAL) constitutes a family of neuropeptides composed of four peptides: (i) galanin (GAL), (ii) galanin-message associated peptide (GAMP), (iii) galanin-like peptide (GALP), and (iv) alarin. GAL contains 29/30 amino acids, and its biological action occurs through the interactions with its various receptors (GALR1, GALR2, and GALR3). The neuropeptide GAL regulates several physiological and pathophysiological functions in the central nervous system, the peripheral nervous system, and the peripheral organs. GAL is secreted mainly by oligodendrocytes, astrocytes, and the gastrointestinal tract, and its effect depends on the interaction with its different receptors. These receptors are expressed mainly in the central, peripheral nervous systems and the intestines. Objective: The present review evaluates the role of GAL family in inflammatory diseases. An overview is given of the signaling and pharmacological effects due to the interaction between GAL and GALR in different cell types. The potential use of GAL as a therapeutic resource is critically discussed. Conclusion: GAL is suggested to have an anti-inflammatory function in some situations and a proinflammatory function in others. The literature on GAL is controversial and currently not conclusive. This could be due to the complexity of the metabolic network signaling induced by the interactions between GAL and GALR. In the next future, GAL might be a promising therapeutic resource for several diseases, but its practical use for disease control is presently not advisable.

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12

Constantin, Stephanie, and Susan Wray. "Galanin Activates G Protein Gated Inwardly Rectifying Potassium Channels and Suppresses Kisspeptin-10 Activation of GnRH Neurons." Endocrinology 157, no. 8 (June 30, 2016): 3197–212. http://dx.doi.org/10.1210/en.2016-1064.

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GnRH neurons are regulated by hypothalamic kisspeptin neurons. Recently, galanin was identified in a subpopulation of kisspeptin neurons. Although the literature thoroughly describes kisspeptin activation of GnRH neurons, little is known about the effects of galanin on GnRH neurons. This study investigated whether galanin could alter kisspeptin signaling to GnRH neurons. GnRH cells maintained in explants, known to display spontaneous calcium oscillations, and a long-lasting calcium response to kisspeptin-10 (kp-10), were used. First, transcripts for galanin receptors (GalRs) were examined. Only GalR1 was found in GnRH neurons. A series of experiments was then performed to determine the action of galanin on kp-10 activated GnRH neurons. Applied after kp-10 activation, galanin 1–16 (Gal1–16) rapidly suppressed kp-10 activation. Applied with kp-10, Gal1–16 prevented kp-10 activation until its removal. To determine the mechanism by which galanin inhibited kp-10 activation of GnRH neurons, Gal1–16 and galanin were applied to spontaneously active GnRH neurons. Both inhibited GnRH neuronal activity, independent of GnRH neuronal inputs. This inhibition was mimicked by a GalR1 agonist but not by GalR2 or GalR2/3 agonists. Although Gal1–16 inhibition relied on Gi/o signaling, it was independent of cAMP levels but sensitive to blockers of G protein-coupled inwardly rectifying potassium channels. A newly developed bioassay for GnRH detection showed Gal1–16 decreased the kp-10-evoked GnRH secretion below detection threshold. Together, this study shows that galanin is a potent regulator of GnRH neurons, possibly acting as a physiological break to kisspeptin excitation.

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13

Hawes, Jessica J., and Marina R. Picciotto. "Characterization of GalR1, GalR2, and GalR3 immunoreactivity in catecholaminergic nuclei of the mouse brain." Journal of Comparative Neurology 479, no. 4 (November 22, 2004): 410–23. http://dx.doi.org/10.1002/cne.20329.

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14

Kołodziejski, Paweł A., Ewa Pruszyńska-Oszmałek, Marcin Hejdysz, Maciej Sassek, Natalia Leciejewska, Kamil Ziarniak, Jakub Bień, Piotr Ślósarz, Marta Kubiś, and Sebastian Kaczmarek. "Effect of Fasting on the Spexin System in Broiler Chickens." Animals 11, no. 2 (February 17, 2021): 518. http://dx.doi.org/10.3390/ani11020518.

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Spexin (SPX) is a highly conservative peptide hormone containing 14 amino acids and was discovered in 2007 by bioinformatics methods. However, nothing is yet known about its role in the metabolism of birds, including broilers. The aim of this study was to investigate the effect of short-term fasting (2, 4, and 8 h) on the concentration of SPX in blood serum and the expression levels of the genes encoding this peptide (SPX1) and its receptors, GALR2 and GALR3, in the tissues involved in carbohydrate and lipid metabolism (muscles, adipose tissue, and liver). We also analyzed the mRNA expression of these genes in various chicken tissues. Moreover, we studied the correlation between the serum level of SPX and other metabolic parameters (insulin, glucagon, glucose, triglycerides, and cholesterol). Using RT-qPCR, we found that SPX1, GALR2, and GALR3 are expressed in all investigated tissues in broiler chicken. Moreover, using a commercially available radio-immunoassay, we noted an increase of the SPX level in blood serum after 4 and 8 h of fasting compared to nonfasted animals (p < 0.05). This increase was positively correlated with glucagon concentration (r = 0.341; p < 0.05) and negatively with glucose concentration (r = −0.484; p < 0.01). Additionally, we discovered that in the short term, food deprivation leads to the expression regulation of SPX1, GALR2, and GLAR3 in tissues associated with metabolism of carbohydrates and lipids. The obtained results indicate that SPX is involved in the regulation of metabolism in broiler chickens.

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15

Wąsowicz, Krzysztof, Piotr Podlasz, Małgorzata Chmielewska, Katarzyna Łosiewicz, Jerzy Kaleczyc, Jacek Żmudzki, Michał Załęcki, Zenon Pidsudko, and Mirosław Łakomy. "Changes in the expression of galanin and galanin receptors in the wall of the colon in pigs experimentally infected with Brachyspira hyodysenteriae." Bulletin of the Veterinary Institute in Pulawy 58, no. 1 (March 1, 2014): 23–28. http://dx.doi.org/10.2478/bvip-2014-0004.

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Abstract The expression of galanin (GAL) and its three receptors (GalR1, GalR2, and GalR3) were studied with real-time PCR in the colonic wall of pigs suffering from experimental colitis caused by the infection with Brachyspira hyodysenteriae. The expression was studied in the muscular membrane, mucosa/submucosa layer, and in lymphocytes isolated from mucosa/submucosa. The expression levels were normalized to glyceraldehyde-6-phosphate dehydrogenase (GAPDH) expression and compared to expression levels in control animals. GAL expression was found in all three studied compartments of the colonic wall. A significant decrease in GAL expression level was found in the mucosa/submucosa and in isolated lymphocytes, whereas the decrease was much less profound in the muscular membrane. In the case of galanin receptors their expression was found in all studied compartments of the colonic wall, however at different levels, as compared to GAPDH expression. The decrease of galanin receptors expression was found in all studied compartments of the colonic wall of the sick animals.

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16

Yue, Hai-Yuan, Tsugumi Fujita, and Eiichi Kumamoto. "Biphasic modulation by galanin of excitatory synaptic transmission in substantia gelatinosa neurons of adult rat spinal cord slices." Journal of Neurophysiology 105, no. 5 (May 2011): 2337–49. http://dx.doi.org/10.1152/jn.00991.2010.

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Although intrathecally administrated galanin modulates nociceptive transmission in a biphasic manner, this has not been fully examined previously. In the present study, the action of galanin on synaptic transmission in the substantia gelatinosa (SG) neurons of adult rat spinal cord slices was examined, using the whole cell patch-clamp technique. Galanin concentration-dependently increased the frequency of spontaneous excitatory postsynaptic current (EPSC; EC50 = 2.0 nM) without changing the amplitude, indicating a presynaptic effect. This effect was reduced in a Ca2+-free, or voltage-gated Ca2+ channel blocker La3+-containing Krebs solution and was produced by a galanin type-2/3 receptor (GalR2/R3) agonist, galanin 2–11, but not by a galanin type-1 receptor (GalR1) agonist, M617. Galanin also concentration-dependently produced an outward current at −70 mV (EC50 = 44 nM), although this appeared to be contaminated by a small inward current. This outward current was mimicked by M617, but not by galanin 2–11. Moreover, galanin reduced monosynaptic Aδ-fiber- and C-fiber-evoked EPSC amplitude; the former reduction was larger than the latter. A similar action was produced by galanin 2–11, but not by M617. Spontaneous and focally evoked inhibitory (GABAergic and glycinergic) transmission was unaffected by galanin. These findings indicate that galanin at lower concentrations enhances the spontaneous release of l-glutamate from nerve terminals by Ca2+ entry from the external solution following GalR2/R3 activation, whereas galanin at higher concentrations also produces a membrane hyperpolarization by activating GalR1. Moreover, galanin reduces l-glutamate release onto SG neurons from primary afferent fibers by activating GalR2/R3. These effects could partially contribute to the behavioral effect of galanin.

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Whitelaw, Christine Margaret, Jane Elizabeth Robinson, George Ballantine Chambers, Peter Hastie, Vasantha Padmanabhan, Robert Charles Thompson, and Neil Price Evans. "Expression of mRNA for galanin, galanin-like peptide and galanin receptors 1–3 in the ovine hypothalamus and pituitary gland: effects of age and gender." REPRODUCTION 137, no. 1 (January 2009): 141–50. http://dx.doi.org/10.1530/rep-08-0266.

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The neurotransmitters/neuromodulators galanin (GAL) and galanin-like peptide (GALP) are known to operate through three G protein-coupled receptors, GALR1, GALR2 and GALR3. The aim of this study was to investigate changes in expression of mRNA for galanin, GALP and GALR1–3 in the hypothalamus and pituitary gland, of male and female sheep, to determine how expression changed in association with growth and the attainment of reproductive competence. Tissue samples from the hypothalami and pituitary glands were analysed from late foetal and pre-pubertal lambs and adult sheep. Although mRNA for galanin and GALR1-3 was present in both tissues, at all ages and in both genders, quantification of GALP mRNA was not possible due to its low levels of expression. mRNA expression for both galanin and its receptors was seen to change significantly in both tissues as a function of age. Specifically, hypothalamic galanin mRNA expression increased with age in the male, but decreased with age in the female pituitary gland. mRNA expression for all receptors increased between foetal and pre-pubertal age groups and decreased significantly between pre-pubertal and adult animals. The results indicate that the expression of mRNA for galanin and its receptors changes dynamically with age and those significant differences exist with regard to tissue type and gender. These changes suggest that galaninergic neuroendocrine systems could be involved in the regulation of ovine growth and or the development of reproductive competence. The roles played by these systems in the sheep, however, may differ from other species, in particular the neuroendocrine link between nutrition and reproduction and GALR1's role in pituitary signalling.

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An, Ke, Yingpeng Cui, Xiaolong Zhong, Kunhe Li, Jinjun Zhang, Huiping Liu, and Zhishuang Wen. "Immortalized Bone Mesenchymal Stromal Cells With Inducible Galanin Expression Produce Controllable Pain Relief in Neuropathic Rats." Cell Transplantation 31 (January 2022): 096368972211038. http://dx.doi.org/10.1177/09636897221103861.

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Management of chronic pain is one of the most difficult problems in modern practice. Grafted human telomerase reverse transcriptase–immortalized bone marrow mesenchymal stromal cells (hTERT-BMSCs) with inducible galanin (GAL) expression have been considered to be a potentially safe and controllable approach for the alleviation of chronic pain. Therefore, in this study, we aimed to assess the feasibility of hTERT-BMSCs/Tet-on/GAL cells secreting GAL under the transcriptional control of doxycycline (Dox) for controllable pain relief. After transplanted into the subarachnoid space of neuropathic rats induced by spared nerve injury of sciatic nerve, their analgesic actions were investigated by behavioral tests. The results showed that the pain-related behaviors, mechanical allodynia, and thermal hyperalgesia were significantly alleviated during 1 to 7 weeks after grafts of hTERT-BMSCs/Tet-on/GAL cells without motor incoordination. Importantly, these effects could be reversed by GAL receptor antagonist M35 and regulated by Dox induction as compared with control. Moreover, the GAL level in cerebrospinal fluid and spinal GAL receptor 1 (GalR1) expression were correlated with Dox administration, but not GAL receptor 2 (GalR2). Meanwhile, spinal protein kinase Mζ (PKMζ) expression was also inhibited significantly. Taken together, these data suggest that inducible release of GAL from transplanted cells was able to produce controllable pain relief in neuropathic rats via inhibiting the PKMζ activation and activating its GalR1 rather than GalR2. This provides a promising step toward a novel stem cell–based strategy for pain therapy.

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Wang, Suke, Tanaz Hashemi, Steven Fried, Anthony L. Clemmons, and Brian E. Hawes. "Differential Intracellular Signaling of the GalR1 and GalR2 Galanin Receptor Subtypes." Biochemistry 37, no. 19 (May 1998): 6711–17. http://dx.doi.org/10.1021/bi9728405.

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20

Lu, Xiaoying, and Tamas Bartfai. "Analyzing the validity of GalR1 and GalR2 antibodies using knockout mice." Naunyn-Schmiedeberg's Archives of Pharmacology 379, no. 4 (January 22, 2009): 417–20. http://dx.doi.org/10.1007/s00210-009-0394-z.

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21

Millón, Carmelo, Flores-Burgess Antonio, Narvaez Manuel, O. Borroto-Escuela Dasiel, Santín Luis, Parrado Concención, Narvaez Jose Angel, Fuxe Kjell, and Diaz-Cabiale Zaida. "GALR1/GALR2 Knockdown rats block the Depression and Anxiogenic effects induced by GAL(1-15): The Heterodimer GALR1/GALR2 as a target of GAL(1-15)." Neuropeptides 65 (October 2017): 151. http://dx.doi.org/10.1016/j.npep.2017.02.074.

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22

Ho, John Chi Wang, Tim Jacobs, Yajun Wang, and Frederick C. Leung. "Identification and characterization of the chicken galanin receptor GalR2 and a novel GalR2-like receptor (GalR2-L)." General and Comparative Endocrinology 179, no. 2 (November 2012): 305–12. http://dx.doi.org/10.1016/j.ygcen.2012.09.005.

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Wang, Peng, Hui Li, Swapnali Barde, Ming-Dong Zhang, Jing Sun, Tong Wang, Pan Zhang, et al. "Depression-like behavior in rat: Involvement of galanin receptor subtype 1 in the ventral periaqueductal gray." Proceedings of the National Academy of Sciences 113, no. 32 (July 25, 2016): E4726—E4735. http://dx.doi.org/10.1073/pnas.1609198113.

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The neuropeptide galanin coexists in rat brain with serotonin in the dorsal raphe nucleus and with noradrenaline in the locus coeruleus (LC), and it has been suggested to be involved in depression. We studied rats exposed to chronic mild stress (CMS), a rodent model of depression. As expected, these rats showed several endophenotypes relevant to depression-like behavior compared with controls. All these endophenotypes were normalized after administration of a selective serotonin reuptake inhibitor. The transcripts for galanin and two of its receptors, galanin receptor 1 (GALR1) and GALR2, were analyzed with quantitative real-time PCR using laser capture microdissection in the following brain regions: the hippocampal formation, LC, and ventral periaqueductal gray (vPAG). Only Galr1 mRNA levels were significantly increased, and only in the latter region. After knocking down Galr1 in the vPAG with an siRNA technique, all parameters of the depressive behavioral phenotype were similar to controls. Thus, the depression-like behavior in rats exposed to CMS is likely related to an elevated expression of Galr1 in the vPAG, suggesting that a GALR1 antagonist could have antidepressant effects.

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Kolakowski, Lee F., Gary P. O'Neill, Andrew D. Howard, Suzanne R. Broussard, Kathleen A. Sullivan, Scott D. Feighner, Marek Sawzdargo, et al. "Molecular Characterization and Expression of Cloned Human Galanin Receptors GALR2 and GALR3." Journal of Neurochemistry 71, no. 6 (November 13, 2002): 2239–51. http://dx.doi.org/10.1046/j.1471-4159.1998.71062239.x.

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WANG, SUKE, TANAZ HASHEMI, STEVEN FRIED, ANTHONY L. CLEMMONS, and BRIAN E. HAWES. "Differential G-Protein-Coupling Profiles of the GalR1 and GalR2 Galanin Receptors." Annals of the New York Academy of Sciences 863, no. 1 GALANIN (December 1998): 457–58. http://dx.doi.org/10.1111/j.1749-6632.1998.tb10723.x.

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Wong, Matthew K. H., Yuan Chen, Mulan He, Chengyuan Lin, Zhaoxiang Bian, and Anderson On-Lam Wong. "Spexin as a Satiety Factor in Mouse via Regulatory Actions Within the Hypothalamus." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A57—A58. http://dx.doi.org/10.1210/jendso/bvab048.116.

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Abstract Spexin (SPX) is a pleiotropic peptide with highly conserved protein sequence from fish to mammals and its biological actions are mediated by GalR2/GalR3 receptors expressed in target tissues. Recently, SPX was found to be a novel satiety factor in fish models but whether the peptide has a similar function in mammals is still unknown. Using the mouse as a model for mammalian species, the functional role of SPX in feeding control and the mechanisms involved were investigated. After food intake, serum SPX could be up-regulated in mice with parallel elevations of transcript expression and tissue content of SPX in the glandular stomach but not in other tissues examined. As revealed by immunostaining, food intake also intensified SPX signals in different cell types within the gastric mucosa of glandular stomach. Furthermore, IP injection of SPX was effective in reducing food consumption with parallel drops in transcript expression of NPY, AgRP, NPY type 5 receptor (NPY5R) and ghrelin receptor (GHSR) in the hypothalamus, and these inhibitory effects could be blocked by GalR3 but not GalR2 antagonism. In agreement with the central actions of SPX, similar inhibition on food intake and hypothalamic expression of NPY, AgRP, NPY5R and GHSR could be observed with ICV injection of SPX. In the same study, parallel rises of transcript expression of leptin receptor (LepR) and melanocortin 4 receptor (MC4R) were also observed in the hypothalamus. These findings, taken together, suggest that the role of SPX as a satiety factor is well-conserved in the mouse. Probably, food consumption can induce SPX production in glandular stomach and contribute to the postprandial rise of SPX in circulation. Through GalR3 activation, this SPX signal can act within the hypothalamus to trigger feedback inhibition on food intake by differential modulation of the feeding regulators (NPY & AgRP) and their receptors (NPY5R, GHSR, LepR & MC4R) involved in the feeding circuitry of the brain.

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Borroto-Escuela, Dasiel O., Patrizia Ambrogini, Manuel Narvaez, Valentina Di Liberto, Sarah Beggiato, Luca Ferraro, Ramon Fores-Pons, et al. "Serotonin Heteroreceptor Complexes and Their Integration of Signals in Neurons and Astroglia—Relevance for Mental Diseases." Cells 10, no. 8 (July 27, 2021): 1902. http://dx.doi.org/10.3390/cells10081902.

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The heteroreceptor complexes present a novel biological principle for signal integration. These complexes and their allosteric receptor–receptor interactions are bidirectional and novel targets for treatment of CNS diseases including mental diseases. The existence of D2R-5-HT2AR heterocomplexes can help explain the anti-schizophrenic effects of atypical antipsychotic drugs not only based on blockade of 5-HT2AR and of D2R in higher doses but also based on blocking the allosteric enhancement of D2R protomer signaling by 5-HT2AR protomer activation. This research opens a new understanding of the integration of DA and 5-HT signals released from DA and 5-HT nerve terminal networks. The biological principle of forming 5-HT and other heteroreceptor complexes in the brain also help understand the mechanism of action for especially the 5-HT hallucinogens, including putative positive effects of e.g., psilocybin and the indicated prosocial and anti-stress actions of MDMA (ecstasy). The GalR1-GalR2 heterodimer and the putative GalR1-GalR2-5-HT1 heteroreceptor complexes are targets for Galanin N-terminal fragment Gal (1–15), a major modulator of emotional networks in models of mental disease. GPCR-receptor tyrosine kinase (RTK) heteroreceptor complexes can operate through transactivation of FGFR1 via allosteric mechanisms and indirect interactions over GPCR intracellular pathways involving protein kinase Src which produces tyrosine phosphorylation of the RTK. The exciting discovery was made that several antidepressant drugs such as TCAs and SSRIs as well as the fast-acting antidepressant drug ketamine can directly bind to the TrkB receptor and provide a novel mechanism for their antidepressant actions. Understanding the role of astrocytes and their allosteric receptor–receptor interactions in modulating forebrain glutamate synapses with impact on dorsal raphe-forebrain serotonin neurons is also of high relevance for research on major depressive disorder.

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Mirchandani-Duque, Marina, Miguel A. Barbancho, Alexander López-Salas, Jose Erik Alvarez-Contino, Natalia García-Casares, Kjell Fuxe, Dasiel O. Borroto-Escuela, and Manuel Narváez. "Galanin and Neuropeptide Y Interaction Enhances Proliferation of Granule Precursor Cells and Expression of Neuroprotective Factors in the Rat Hippocampus with Consequent Augmented Spatial Memory." Biomedicines 10, no. 6 (June 1, 2022): 1297. http://dx.doi.org/10.3390/biomedicines10061297.

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Dysregulation of hippocampal neurogenesis is linked to several neurodegenereative diseases, where boosting hippocampal neurogenesis in these patients emerges as a potential therapeutic approach. Accumulating evidence for a neuropeptide Y (NPY) and galanin (GAL) interaction was shown in various limbic system regions at molecular-, cellular-, and behavioral-specific levels. The purpose of the current work was to evaluate the role of the NPY and GAL interaction in the neurogenic actions on the dorsal hippocampus. We studied the Y1R agonist and GAL effects on: hippocampal cell proliferation through the proliferating cell nuclear antigen (PCNA), the expression of neuroprotective and anti-apoptotic factors, and the survival of neurons and neurite outgrowth on hippocampal neuronal cells. The functional outcome was evaluated in the object-in-place task. We demonstrated that the Y1R agonist and GAL promote cell proliferation and the induction of neuroprotective factors. These effects were mediated by the interaction of NPYY1 (Y1R) and GAL2 (GALR2) receptors, which mediate the increased survival and neurites’ outgrowth observed on neuronal hippocampal cells. These cellular effects are linked to the improved spatial-memory effects after the Y1R agonist and GAL co-injection at 24 h in the object-in-place task. Our results suggest the development of heterobivalent agonist pharmacophores, targeting Y1R–GALR2 heterocomplexes, therefore acting on the neuronal precursor cells of the DG in the dorsal hippocampus for the novel therapy of neurodegenerative cognitive-affecting diseases.

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Borroto-Escuela, Dasiel O., Manuel Narvaez, Michael Di Palma, Feliciano Calvo, David Rodriguez, Carmelo Millon, Jens Carlsson, et al. "Preferential activation by galanin 1–15 fragment of the GalR1 protomer of a GalR1–GalR2 heteroreceptor complex." Biochemical and Biophysical Research Communications 452, no. 3 (September 2014): 347–53. http://dx.doi.org/10.1016/j.bbrc.2014.08.061.

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Hawes, Jessica J., Darlene H. Brunzell, David Wynick, Venetia Zachariou, and Marina R. Picciotto. "GalR1, but not GalR2 or GalR3, levels are regulated by galanin signaling in the locus coeruleus through a cyclic AMP-dependent mechanism." Journal of Neurochemistry 93, no. 5 (April 7, 2005): 1168–76. http://dx.doi.org/10.1111/j.1471-4159.2005.03105.x.

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31

Lioudyno, Victoria I., Alexandr G. Ilves, Gennadij N. Bisaga, and Irina N. Abdurasulova. "Multiple sclerosis progression and galanin receptor GALR2: is there evidence for a link?" Medical academic journal 21, no. 2 (September 24, 2021): 107–11. http://dx.doi.org/10.17816/maj75854.

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BACKGROUND: Given the recently proposed role of the rare galanin receptor-2 (GALR2) genes missense mutation (SNP rs61745847) in the etiology of MS, we genotyped rs61745847 in a group of MS patients that was enriched with an unfavorable disease course cases. MATERIALS AND METHODS: Our study cohort consisted of 100 MS patients selected based on their progressive course, high disease progression rate and pediatric onset. To determine the nucleotide sequence of GALR2 gene fragment, surrounding the rs61745847 area, Sanger sequencing of PCR amplicons was performed. RESULTS: No homozygous rs61745847 carrier was found in our cohort, and the region of exon 2 surrounding rs61745847 completely coincided with the reference sequence (Gene Bank NC_000017.11). In agreement with previously published data on Canadian and Brazilian populations of patients, our study of a Russian cohort confirmed the rarity of the rs61745847 variant, including among patients with rapidly progressive MS. CONCLUSIONS: Thus, although structural changes in the GALR2 gene associated with rs61745847 may play a significant role in individual patients carrying this rare mutation, it is unlikely that such changes determine an unfavorable disease course of MS in general.

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Anderson, Maria E., Johan Runesson, Indrek Saar, Ülo Langel, and John K. Robinson. "Galanin, through GalR1 but not GalR2 receptors, decreases motivation at times of high appetitive behavior." Behavioural Brain Research 239 (February 2013): 90–93. http://dx.doi.org/10.1016/j.bbr.2012.10.045.

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Hall, Jerica R., Mara Hirchert, Kasey R. Maddock Carlin, Carl R. Dahlen, and Alison K. Ward. "PSV-20 The effect of differing implant strategies on the galanin receptor 2 genotype on feed intake, efficiency, and feeding behavior of crossbred Angus finishing steers." Journal of Animal Science 98, Supplement_3 (November 2, 2020): 159. http://dx.doi.org/10.1093/jas/skaa054.280.

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Abstract Abstract: The objective of this study was to determine how the interaction different implant strategies with the galanin receptor 2 (GALR2) would influence intake, efficiency, and feeding behavior of finishing steers along with carcass characteristics. Angus crossbred steers (n = 93) were selected for this study based on their GALR2 genotype (GG, TT, and TG) and weaning weight with 19 GG, 36 TT, and 38 TG. Calves were blocked by initial body weight and fed a standard feedlot ration for 166 d or 202 d. Body weight data and blood samples were collected every 28 d. Steers were randomly assigned to one of two implant strategies; 1) a single Revalor-S (Merk, New Jersey) on d 77, or 2) a Revalor-S with on d 0 and another on d 77. Intake and feeding behavior data were recorded using RFID tags and Insentec feeders (Hokofarm Group, B.V., Marknesse, the Netherlands). Total DMI and feeding behavior were summarized following procedures described by (Swanson et al. 2014). Data were analyzed using the mixed procedure in SAS with a 2 x 3 factorial arrangement of treatments. The interaction of genotype x implant had a significant effect on minutes spent eating/visit (P = 0.02). The main effect of genotype had a significant effect on DMI (P = 0.05), number of meals/day (P 0.0001), and intake/minute (P = 0.002). While there was a greater DMI with the GG genotype we do not see the benefit of improved feed efficiency. The main effect of implant had a significant effect on ADG (P = 0.0008) and intake/visit (P 0.0012). Based on this data we conclude that there is no interaction between GALR2 genotype and implant strategy on efficiency or intake in finishing steers, however there may be benefit to future studies focusing on the GALR2 genotype and intake.

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Anderson, Ellie S., Jerica R. Hall, Mara R. Hirchert, Kendall C. Swanson, Kasey R. Maddock Carlin, Carl R. Dahlen, and Alison K. Ward. "PSIII-11 The effect of GALR2 genotype and differing implant strategies on blood metabolite concentrations in finishing steers." Journal of Animal Science 98, Supplement_3 (November 2, 2020): 239. http://dx.doi.org/10.1093/jas/skaa054.419.

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Abstract The neuropeptide receptor galanin receptor 2 (GALR2) is involved in appetite regulation and is therefore a potential target for marker-assisted management of finishing cattle. The objective of this study was to determine the interaction between implant strategy and GALR2 genotype on the metabolic status of feedlot steers. Angus crossbred steers (n = 93) were selected for the study based on GALR2 c.-199G >T genotype (n = 19 GG, 36 TT and 38 TG steers). Steers were blocked by initial body weight into two groups (248 ± 50 and 293± 43 kg) and finished for 166 or 202 days. Steers were assigned one of two implant strategies in a 2 (implant) × 3 (genotype) factorial design. The implant strategies were: one implant of Revalor-S (Merk, New Jersey) on day 77 of finishing (1X) or two implants with the first on day 0 and the second on day 77 (2X). All steers were fed a standard feedlot ration throughout the study. Blood samples were collected every 28 days. Serum samples were analyzed for blood urea nitrogen (BUN) and glucose concentration. Data were analyzed using the mixed procedure of SAS with repeated measures and significance was set at P < 0.05. Day × Implant interaction had a significant effect on BUN (P = 0.0035), and day × genotype had a significant effect on serum glucose concentration (P = 0.0049). There was no effect of implant × genotype interaction for BUN or glucose (P > 0.05). On days 84 and 140 glucose concentration was greater in GG steers than GT steers (P < 0.05) and tended to be greater than TT steers (P ≤ 0.0667). We conclude that there is no interaction between implant strategy and GALR2 genotype on metabolism in finishing steers.

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Runesson, Johan, Indrek Saar, Linda Lundström, Jaak Järv, and Ülo Langel. "A novel GalR2-specific peptide agonist." Neuropeptides 43, no. 3 (June 2009): 187–92. http://dx.doi.org/10.1016/j.npep.2009.04.004.

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Pang, Ling, Michael Graziano, and Suke Wang. "Membrane Cholesterol Modulates Galanin−GalR2 Interaction." Biochemistry 38, no. 37 (September 1999): 12003–11. http://dx.doi.org/10.1021/bi990227a.

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37

Barreto, Savio G., Charmaine M. Woods, Colin J. Carati, Ann C. Schloithe, Surendra R. Jaya, James Toouli, and Gino T. P. Saccone. "Galanin inhibits caerulein-stimulated pancreatic amylase secretion via cholinergic nerves and insulin." American Journal of Physiology-Gastrointestinal and Liver Physiology 297, no. 2 (August 2009): G333—G339. http://dx.doi.org/10.1152/ajpgi.00078.2009.

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Pancreatic exocrine secretion is affected by galanin, but the mechanisms involved are unclear. We aimed to determine the effect and elucidate the mechanism of action of exogenous galanin on basal and stimulated pancreatic amylase secretion in vitro. The effect of galanin on basal-, carbachol-, and caerulein-stimulated amylase secretion from isolated murine pancreatic lobules was measured. Carbachol and caerulein concentration-response relationships were established. Lobules were coincubated with galanin (10−12 M to 10−7 M), carbachol (10−6 M), or caerulein (10−10 M). Lobules were preincubated with atropine (10−5 M), tetrodotoxin (10−5 M), hexamethonium (10−5 M), or diazoxide (10−7 M and 10−4 M) for 30 min followed by incubation with caerulein (10−10 M) alone or combined with galanin (10−12 M). Amylase secretion was expressed as percent of total lobular amylase. Immunohistochemical studies used the antigen retrieval technique and antisera for galanin receptor (GALR) 1, 2, and 3. Carbachol and caerulein stimulated amylase secretion in a concentration-dependent manner with maximal responses of two- and 1.7-fold over control evoked at 10−6 M and 10−10 M, respectively. Galanin (10−12 M) completely inhibited caerulein-stimulated amylase secretion but had no effect on carbachol-stimulated or basal secretion. Atropine and tetrodotoxin pretreatment abolished the caerulein-stimulated amylase secretion, whereas hexamethonium had no significant effect. Diazoxide significantly reduced caerulein-stimulated amylase secretion by ∼80%. Galanin did not affect caerulein-stimulated amylase secretion in the presence of hexamethonium or diazoxide. Glucose-stimulated amylase secretion was also inhibited by galanin. Immunohistochemistry revealed islet cells labeled for GALR2. These data suggest that galanin may modulate caerulein-stimulated amylase secretion by acting on cholinergic nerves and/or islet cells possibly via GALR2 to regulate insulin release.

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Heo, Yunseok, Naito Ishimoto, Ye-Eun Jeon, Ji-Hye Yun, Mio Ohki, Yuki Anraku, Mina Sasaki, et al. "Structure of the human galanin receptor 2 bound to galanin and Gq reveals the basis of ligand specificity and how binding affects the G-protein interface." PLOS Biology 20, no. 8 (August 1, 2022): e3001714. http://dx.doi.org/10.1371/journal.pbio.3001714.

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Galanin is a neuropeptide expressed in the central and peripheral nervous systems, where it regulates various processes including neuroendocrine release, cognition, and nerve regeneration. Three G-protein coupled receptors (GPCRs) for galanin have been discovered, which is the focus of efforts to treat diseases including Alzheimer’s disease, anxiety, and addiction. To understand the basis of the ligand preferences of the receptors and to assist structure-based drug design, we used cryo-electron microscopy (cryo-EM) to solve the molecular structure of GALR2 bound to galanin and a cognate heterotrimeric G-protein, providing a molecular view of the neuropeptide binding site. Mutant proteins were assayed to help reveal the basis of ligand specificity, and structural comparison between the activated GALR2 and inactive hβ2AR was used to relate galanin binding to the movements of transmembrane (TM) helices and the G-protein interface.

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Hall, Jerica R., Kasey Maddock-Carlin, Carl R. Dahlen, and Alison K. Ward. "168 Effects of GALR2 genotype and differing implant strategies on carcass characteristics of crossbred Angus finishing steers." Journal of Animal Science 98, Supplement_4 (November 3, 2020): 126. http://dx.doi.org/10.1093/jas/skaa278.230.

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Abstract The objective of this study was to determine how the interaction of different implant strategies with the galanin receptor 2 (GALR2) genotype would affect carcass characteristics and meat quality in crossbred Angus finishing steers. Angus crossbred steers (n = 93) were selected for this study based on their GALR2c.-199T > G genotype (GG, TT, and TG) and weaning weight with 19 GG, 38 TG, and 36 TT. Calves were blocked by initial body weight and fed a standard feedlot ration for 166 d or 202 d. Body weight data and blood samples were collected every 28 d. Steers were randomly assigned to one of two implant strategies: 1) a single Revalor-S (Merk Animal Health, NJ) on d 77 (1×), or 2) a Revalor-S on d 0 and another on d 77 (2×). Data were analyzed as a 2 × 3 factorial design of implant strategy by GALR2c.-199T > G genotype using the mixed procedure in SAS, with repeated measures used for color, and significance was set at P < 0.05. Hot carcass weight and back fat were directly affected by implant strategy where steers on the 2 implant strategy exhibited heavier hot carcass weights and increased back fat (P < 0.05). Cook loss and shear force were influenced by the interaction of genotype by implant strategy (P < 0.05). The GG steers exhibited less cook loss in comparison to all other treatments. The GG steers exhibited the highest shear force value of all treatments. The pH, water holding capacity, and color of the striploins were not affected by the genotype by implant strategy interaction or main effects of genotype and implant strategy. From this we conclude the interaction of GALR2c.-199T >G genotype implant strategy does not have a negative effect on carcass characteristics or meat quality in crossbred Angus finishing steers.

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O'Donnell, Dajan, Sultan Ahmad, Claes Wahlestedt, and Philippe Walker. "Expression of the novel galanin receptor subtype GALR2 in the adult rat CNS: Distinct distribution from GALR1." Journal of Comparative Neurology 409, no. 3 (July 5, 1999): 469–81. http://dx.doi.org/10.1002/(sici)1096-9861(19990705)409:3<469::aid-cne10>3.0.co;2-q.

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41

Lv, Shuangyu, Yuchen Zhou, Yu Feng, Xiaomei Zhang, Xinyue Wang, Yanjie Yang, and Xinchun Wang. "Peripheral Spexin Inhibited Food Intake in Mice." International Journal of Endocrinology 2020 (August 5, 2020): 1–9. http://dx.doi.org/10.1155/2020/4913785.

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Spexin (SPX, NPQ), a novel endogenous neuropeptide, was firstly identified by bioinformatics. Spexin gene and protein widely distributed in the central nervous system and peripheral tissues, such as the hypothalamus and digestive tract. The role of spexin in appetite regulation in mammalian is still unclear. The present study was designed to investigate the mechanism and effect of peripheral spexin on food intake in mice. During the light period, an intraperitoneal (i.p.) injection of spexin (10 nmol/mouse) significantly inhibited cumulative food intake at 2, 4, and 6 h after treatment in fasted mice. During the dark period, spexin (1 and 10 nmol/mouse, i.p.) significantly suppressed cumulative food intake at 4 and 6 h after treatment in freely feeding mice. The GALR3 antagonist SNAP37889, not GALR2 antagonist, significantly antagonized the inhibitory effect on cumulative food intake (0–6 h) induced by spexin. Spexin significantly reduced the mRNA level of Npy mRNA, not Agrp, Pomc, Cart, Crh, Orexin, or Mch, in the hypothalamus. Spexin (10 nmol/mouse, i.p.) increased the number of c-Fos positive neurons in hypothalamic AHA and SCN, but not in ARC, DMN, LHA, PVN, SON, or VMH. The hypothalamic p-CaMK2 protein expression was upregulated by spexin. This study indicated that acute peripheral injection of spexin inhibited mouse food intake. The anorectic effect may be mediated by GALR3, and inhibiting neuropeptide Y (NPY) via p-CaMK2 and c-Fos in the hypothalamus.

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Robertson, Charles R., Erika Adkins Scholl, Timothy H. Pruess, Brad R. Green, H. Steve White, and Grzegorz Bulaj. "Engineering Galanin Analogues That Discriminate between GalR1 and GalR2 Receptor Subtypes and Exhibit Anticonvulsant Activity following Systemic Delivery." Journal of Medicinal Chemistry 53, no. 4 (February 25, 2010): 1871–75. http://dx.doi.org/10.1021/jm9018349.

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43

Borroto Escuela, D. O., F. Calvo, M. Narvaez, W. Romero-Fernandez, C. Millon, M. Di Palma, M. Pérez-Alea, et al. "P.1.g.067 The GalR1–GalR2 heteroreceptor complex can be the receptor for galanin fragment 1–15." European Neuropsychopharmacology 24 (October 2014): S242—S243. http://dx.doi.org/10.1016/s0924-977x(14)70378-5.

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44

Encarnacion, Mary, Cecily Q. Bernales, Anthony L. Traboulsee, A. Dessa Sadovnick, and Carles Vilariño-Güell. "Analysis of galanin receptor GALR2 in multiple sclerosis." Pharmacogenomics Journal 19, no. 6 (October 14, 2019): 499–500. http://dx.doi.org/10.1038/s41397-019-0100-6.

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45

Zalecki, Michal, Waldemar Sienkiewicz, Amelia Franke-Radowiecka, Magdalena Klimczuk, and Jerzy Kaleczyc. "The Influence of Gastric Antral Ulcerations on the Expression of Galanin and GalR1, GalR2, GalR3 Receptors in the Pylorus with Regard to Gastric Intrinsic Innervation of the Pyloric Sphincter." PLOS ONE 11, no. 5 (May 13, 2016): e0155658. http://dx.doi.org/10.1371/journal.pone.0155658.

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46

Borowsky, Beth, Mary W. Walker, Ling-Yan Huang, Kenneth A. Jones, Kelli E. Smith, Jonathan Bard, Theresa A. Branchek, and Christophe Gerald. "Cloning and characterization of the human galanin GALR2 receptor." Peptides 19, no. 10 (January 1998): 1771–81. http://dx.doi.org/10.1016/s0196-9781(98)00133-8.

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47

Bloomquist, Brian T., Michelle R. Beauchamp, Leonid Zhelnin, Su-Ellen Brown, Ann R. Gore-Willse, Paul Gregor, and Linda J. Cornfield. "Cloning and Expression of the Human Galanin Receptor GalR2." Biochemical and Biophysical Research Communications 243, no. 2 (February 1998): 474–79. http://dx.doi.org/10.1006/bbrc.1998.8133.

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48

Šípková, J., P. Šída, N. Kaspříková, I. Kramáriková, S. Hynie, and Věra Klenerová. "Effect of Stress on the Expression of Galanin Receptors in Rat Heart." Folia Biologica 63, no. 3 (2017): 98–104. http://dx.doi.org/10.14712/fb2017063030098.

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Neuropeptide galanin, galanin-like peptide and galanin receptors 1, 2 and 3 are a crucial part of the so-called galaninergic system. Our previous studies have shown the possible role of this system in mood modulation, especially regarding stress. So far, the galanin receptors have been found in different tissues including brain and heart. Our study deals with changes in expression of galanin receptor subtypes in the heart of Wistar rats exposed to three different types of stress. Galanin receptor subtypes were determined in fluorescently labelled samples using specific primary antibodies, and all sections were analysed in an immunofluorescent microscope and microphotographs. Image analyses were subsequently performed by software ImageJ, using the threshold method with calculation of the DAPI/galanin receptor signal ratio. We found all three types of receptors in the right and left atria and left and right ventricles. Changes in the density of galanin receptors after application of the stressor depended on the observed heart compartment. We found a significant decrease of galanin receptor 1 in all compartments after all types of stress. For GalR2 and GalR3, the increase/decrease of density was dependent on the tested compartment. These results show that galanin receptors could be involved in the function of heart during the cardiac cycle.

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49

Wang, Lu, Andy Tran, Juliette Lee, and Denise D. Belsham. "Palmitate differentially regulates Spexin, and its receptors Galr2 and Galr3, in GnRH neurons through mechanisms involving PKC, MAPKs, and TLR4." Molecular and Cellular Endocrinology 518 (December 2020): 110991. http://dx.doi.org/10.1016/j.mce.2020.110991.

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50

Liu, H. X., P. Brumovsky, R. Schmidt, W. Brown, K. Payza, L. Hodzic, C. Pou, C. Godbout, and T. Hokfelt. "Receptor subtype-specific pronociceptive and analgesic actions of galanin in the spinal cord: Selective actions via GalR1 and GalR2 receptors." Proceedings of the National Academy of Sciences 98, no. 17 (July 31, 2001): 9960–64. http://dx.doi.org/10.1073/pnas.161293598.

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