Galanin-receptor ligand M40 peptide distinguishes between putative galanin-receptor subtypes

摘要: Abstract The galanin-receptor ligand M40 [galanin-(1-12)-Pro3-(Ala-Leu)2-Ala amide] binds with high affinity to [mono[125I]iodo-Tyr26]galanin-binding sites in hippocampal, hypothalamic, and spinal cord membranes from Rin m5F rat insulinoma cells (IC50 = 3-15 nM). Receptor autoradiographic studies show that (1 microM) displaces [mono[125I]iodo-Tyr26]galanin binding the hippocampus, hypothalamus, cord. In brain, acts as a potent antagonist: M40, doses comparable of galanin, antagonizes stimulatory effects galanin on feeding, it blocks galaninergic inhibition scopolamine-induced acetylcholine release ventral hippocampus vivo. contrast, completely fails antagonize both galanin-mediated glucose-induced insulin isolated mouse pancreatic islets inhibitory forskolin-stimulated accumulation 3',5'-cAMP cells; instead is weak agonist at receptors these two systems. antagonist flexor reflex model. These results suggest least subtypes receptor may exist. Hypothalamic hippocampal represent putative central subtype (GL-1-receptor) blocked by M40. The another (GL-2-receptor) recognizes but agonist. occupy an intermediate position between subtypes.