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

Academic Article
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Overview

authors

  • Bartfai, Tamas
  • Langel, Ülo
  • Bedecs, K.
  • Andell, S.
  • Land, T.
  • Gregersen, S.
  • Ahren, B.
  • Girotti, P.
  • Consolo, S.
  • Corwin, R.
  • Crawley, J.
  • Xu, X. J.
  • Wiesenfeld-Hallin, Z.
  • Hokfelt, T.

publication date

  • December 1993

journal

  • Proceedings of the National Academy of Sciences of the United States of America  Journal

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 and in membranes from Rin m5F rat insulinoma cells (IC50 = 3-15 nM). Receptor autoradiographic studies show that M40 (1 microM) 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 m5F 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.

subject areas

  • Amino Acid Sequence
  • Animals
  • Binding, Competitive
  • Feeding Behavior
  • Galanin
  • Insulin
  • Ligands
  • Male
  • Molecular Sequence Data
  • Peptide Fragments
  • Peptides
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Galanin
  • Receptors, Gastrointestinal Hormone
  • Secretory Rate
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Research

keywords

  • ACETYLCHOLINE RELEASE
  • FEEDING
  • INSULIN
  • NOCICEPTIVE REFLEX
  • PEPTIDE ANTAGONIST
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Identity

PubMed Central ID

  • PMC47967

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.90.23.11287

PubMed ID

  • 7504301
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Additional Document Info

start page

  • 11287

end page

  • 11291

volume

  • 90

issue

  • 23

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