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

Tamas Bartfai, Ülo Langel, Katarina Bedecs, Siv Andell, Tiit Land, Sören Gregersen, Bo Ahrén, Prisca Girotti, Silvana Consolo, Rebecca Corwin, Jacqueline Crawley, Xiaojun Xu, Zsuzsanna Wiesenfeld-Hallin, Tomas Hökfelt

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

Original languageEnglish (US)
Pages (from-to)11287-11291
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number23
StatePublished - Dec 1 1993

All Science Journal Classification (ASJC) codes

  • General


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