&lt;b&gt;[Ala&lt;sup&gt;6&lt;/sup&gt;, D-Trp&lt;sup&gt;8&lt;/sup&gt;]GALANIN(&lt;i&gt;1-15&lt;/i&gt;)Ol IS A POTENT GALANIN ANTAGONIST ON INSULIN &lt;/b&gt;&lt;b&gt;RELEASE &lt;/b&gt;

Kakuyama, Hiroyoshi; Mochizuki, Tohru; Iguchi, Kazuaki; Yamabe, K.; Hosoe, Hiroaki; Hoshino, Minoru; Yanaihara, Noboru

doi:10.2220/biomedres.18.49

Cited by 9 publications

(2 citation statements)

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“…Galanin, C7, galanin-(1-19), M35, and galanin-(2-29) bound GalR3 with high affinity (within 9-fold K i of galanin), while M40, galanin-(1-16), and M15 bound rGalR3 with relatively lower affinities (33-60 times K i of galanin) ( Table I) (Table I). [Ala 6 ,Trp 8 ]Galanin-(1-15)-ol, an antagonist shown to inhibit the effect of galanin on forskolin-induced insulin release from RINm5F cells (26), bound the GalR3 receptor with high affinity (Table I). When tested in the same competition binding assays, somatostatin, dynorphin (-opioid receptor-specific ligand) and DAGO (-opioid receptor-specific ligand) did not cause detectable displacement of the radioligand.…”

Section: Table Imentioning

confidence: 99%

Cloning and Expressional Characterization of a Novel Galanin Receptor

Wang¹,

He²,

Hashemi³

et al. 1997

Journal of Biological Chemistry

203

100

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Galanin, a 29 -30 amino acid neuropeptide, is found in the central and peripheral nervous systems and displays several important physiological activities. The actions are believed to be mediated through distinct G proteincoupled receptors. To date, two galanin receptor subtypes have been cloned. In this report, we describe the cloning and expression of a cDNA encoding a novel galanin receptor (GalR3). The receptor has 370 amino acids and shares 36 and 54% homology with the rat GalR1 and GalR2 receptors.125 I-Porcine galanin binds the rat GalR3 receptor expressed in COS-7 cells with high affinity (K d ‫؍‬ 0.6 nM) and could be displaced by galanin and galanin fragments and galanin-chimeric peptides. The pharmacological profile of this novel receptor is distinct from those of GalR1 and GalR2, revealing different pharmacophores within galanin for the three galanin receptor subtypes. Northern blot analysis showed expression in heart, spleen, and testis. Unlike GalR1 and GalR2, no expression of GalR3 was detectable in the brain, suggesting that GalR3 may mediate some of the peripheral functions of galanin.Galanin is a 29 -30 amino acid neuropeptide with no significant homology to any known family of biologically active peptides (1). Galanin is widely distributed in the central and peripheral nervous systems and is highly expressed in various regions of the brain. Many physiological processes are modulated by galanin, including neurotransmitter and hormone release (2), spinal reflexes, nociception (3), firing of noradrenergic neurons, and contraction of gastrointestinal smooth muscle (4, 5). Like neuropeptide Y, centrally administered galanin potently stimulates food intake in animals (6), suggesting a role for galanin in control of body weight.A large body of evidence suggests that galanin mediates the various physiological functions through interaction with distinct receptor subtypes. Pharmacological studies with several peptidic agonists and antagonists of galanin receptor suggest the existence of multiple receptor subtypes (7-9). The first of these receptors (GalR1) has been cloned from several species (10 -13). More recently, a second galanin receptor subtype (GalR2) was cloned. GalR2 is markedly dissimilar to the GalR1 receptor, sharing only 40% sequence homology (14,15). Hydropathy analysis suggests that both GalR1 and GalR2 receptors have seven hydrophobic transmembrane domains, typical of members of the G protein-coupled receptor superfamily (16). The GalR2 receptor is distinguished pharmacologically from the GalR1 receptor by its high affinity for ligand galanin-(2-29). In addition to the pharmacological differences, the GalR2 transcript is widely distributed in both central and peripheral tissues (14, 15), whereas the expression of GalR1 is more restricted to brain and spinal cord (12,13).Given that a large number of physiological actions are modulated by galanin, it is unlikely that the two cloned galanin receptors mediate all the functions of galanin. A complete understanding of the roles of galanin requir...

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Section: Table Imentioning

confidence: 99%

Cloning and Expressional Characterization of a Novel Galanin Receptor

Wang¹,

He²,

Hashemi³

et al. 1997

Journal of Biological Chemistry

203

100

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“…This rate of infusion produced an inhibition of basal insulin output that was similar in magnitude but more sustained than that produced by stimulation of the sympathetic nerves of the pancreas. This inhibitory effect of galanin on insulin secretion may be mediated by any of the three currently identified galanin (GAL) receptors (R), since the mRNA for GALRI [15] and GALR2 [16] has been detected in insulinoma cell lines, and since an antagonist impairing the ability of galanm to inhibit insulin secretion [17] binds with high affinity to GALR3 [18]. Thus, local galanin infusion reproduced the insulin inhibitory response to sympathetic nerve stimulation [14], which local NE infusion could not [9].…”

Section: Neural Localization Of Pancreatic Galaninmentioning

confidence: 99%

The Canine Sympathetic Neuropeptide Galanin: A Neurotransmitter in Pancreas, A Neuromodulator in Liver

Taborsky¹,

Dunning²,

Havel³

et al. 1999

Horm Metab Res

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Our laboratory has investigated the role of the neuropeptide galanin in the sympathetic neural control of both the canine endocrine pancreas and liver. Galanin mRNA and peptide were found in the neuronal cell bodies of the celiac ganglion, which projects fibers to both organs. Galanin fibers formed dense networks around the islets. Galanin was released from these nerves and the amount released appeared sufficient to markedly inhibit basal insulin secretion. We therefore propose that galanin is a sympathetic neurotransmitter in canine endocrine pancreas. Galanin was also found in hepatic nerves usually co-localized with tyrosine hydroxylase, a sympathetic marker. Further, intraportal administration of the sympathetic neurotoxin, 6-hydroxydopamine, abolished galanin staining in the hepatic parenchyma. We evaluated the role of galanin in mediating the actions of sympathetic nerves to increase hepatic glucose production and decrease hepatic arterial conductance. Local infusion of synthetic galanin had little effect by itself, but it did potentiate the action of norepinephrine to stimulate hepatic glucose production, demonstrating a neuromodulatory action. In contrast, galanin had no effect on hepatic arterial blood flow. We therefore propose that in the liver galanin functions as a neuromodulator of norepinephrine's metabolic action.

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