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

Research output: Contribution to journalArticle

123 Citations (Scopus)

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 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
Volume90
Issue number23
StatePublished - Dec 1 1993
Externally publishedYes

Fingerprint

Galanin Receptors
Galanin
Ligands
Peptides
Spinal Cord
Hippocampus
Binding Sites
M40
Insulinoma
Scopolamine Hydrobromide
Membranes
Colforsin
Islets of Langerhans
Amides
Hypothalamus
Inhibitory Concentration 50
Acetylcholine
Reflex
Insulin

Keywords

  • Acetylcholine release
  • Feeding
  • Insulin
  • Nociceptive reflex
  • Peptide antagonist

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Bartfai, T., Langel, Ü., Bedecs, K., Andell, S., Land, T., Gregersen, S., ... Hökfelt, T. (1993). Galanin-receptor ligand M40 peptide distinguishes between putative galanin-receptor subtypes. Proceedings of the National Academy of Sciences of the United States of America, 90(23), 11287-11291.

Galanin-receptor ligand M40 peptide distinguishes between putative galanin-receptor subtypes. / Bartfai, Tamas; Langel, Ülo; Bedecs, Katarina; Andell, Siv; Land, Tiit; Gregersen, Sören; Ahrén, Bo; Girotti, Prisca; Consolo, Silvana; Corwin, Rebecca; Crawley, Jacqueline; Xu, Xiaojun; Wiesenfeld-Hallin, Zsuzsanna; Hökfelt, Tomas.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 90, No. 23, 01.12.1993, p. 11287-11291.

Research output: Contribution to journalArticle

Bartfai, T, Langel, Ü, Bedecs, K, Andell, S, Land, T, Gregersen, S, Ahrén, B, Girotti, P, Consolo, S, Corwin, R, Crawley, J, Xu, X, Wiesenfeld-Hallin, Z & Hökfelt, T 1993, 'Galanin-receptor ligand M40 peptide distinguishes between putative galanin-receptor subtypes', Proceedings of the National Academy of Sciences of the United States of America, vol. 90, no. 23, pp. 11287-11291.
Bartfai, Tamas ; Langel, Ülo ; Bedecs, Katarina ; Andell, Siv ; Land, Tiit ; Gregersen, Sören ; Ahrén, Bo ; Girotti, Prisca ; Consolo, Silvana ; Corwin, Rebecca ; Crawley, Jacqueline ; Xu, Xiaojun ; Wiesenfeld-Hallin, Zsuzsanna ; Hökfelt, Tomas. / Galanin-receptor ligand M40 peptide distinguishes between putative galanin-receptor subtypes. In: Proceedings of the National Academy of Sciences of the United States of America. 1993 ; Vol. 90, No. 23. pp. 11287-11291.
@article{37062c207b1940388a0121a7a78dcd04,
title = "Galanin-receptor ligand M40 peptide distinguishes between putative galanin-receptor subtypes",
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 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.",
keywords = "Acetylcholine release, Feeding, Insulin, Nociceptive reflex, Peptide antagonist",
author = "Tamas Bartfai and {\"U}lo Langel and Katarina Bedecs and Siv Andell and Tiit Land and S{\"o}ren Gregersen and Bo Ahr{\'e}n and Prisca Girotti and Silvana Consolo and Rebecca Corwin and Jacqueline Crawley and Xiaojun Xu and Zsuzsanna Wiesenfeld-Hallin and Tomas H{\"o}kfelt",
year = "1993",
month = "12",
day = "1",
language = "English (US)",
volume = "90",
pages = "11287--11291",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "23",

}

TY - JOUR

T1 - Galanin-receptor ligand M40 peptide distinguishes between putative galanin-receptor subtypes

AU - Bartfai, Tamas

AU - Langel, Ülo

AU - Bedecs, Katarina

AU - Andell, Siv

AU - Land, Tiit

AU - Gregersen, Sören

AU - Ahrén, Bo

AU - Girotti, Prisca

AU - Consolo, Silvana

AU - Corwin, Rebecca

AU - Crawley, Jacqueline

AU - Xu, Xiaojun

AU - Wiesenfeld-Hallin, Zsuzsanna

AU - Hökfelt, Tomas

PY - 1993/12/1

Y1 - 1993/12/1

N2 - 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.

AB - 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.

KW - Acetylcholine release

KW - Feeding

KW - Insulin

KW - Nociceptive reflex

KW - Peptide antagonist

UR - http://www.scopus.com/inward/record.url?scp=0027358576&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027358576&partnerID=8YFLogxK

M3 - Article

C2 - 7504301

AN - SCOPUS:0027358576

VL - 90

SP - 11287

EP - 11291

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 23

ER -