N-terminal galanin-(1-16) fragment is an agonist at the hippocampal galanin receptor

G. Fisone, M. Berthold, K. Bedecs, A. Unden, T. Bartfai, R. Bertorelli, S. Consolo, Jacqueline Crawley, B. Martin, S. Nilsson, T. Hokfelt

Research output: Contribution to journalArticle

119 Citations (Scopus)

Abstract

The galanin N-terminal fragment [galanin-(1-16)] has been prepared by solid-phase synthesis and by enzymic cleavage of galanin by endoproteinase Asp-N. This peptide fragment displaced 125I-labeled galanin in receptor autoradiography experiments on rat forebrain and spinal cord and in equilibrium binding experiments from high-affinity binding sites in the ventral hippocampus with an IC50 of ~ 3 nM. In tissue slices of the same brain area, galanin-(1-16), similarly to galanin, inhibited the muscarinic agonist-stimulated breakdown of inositol phospholipids. Upon intracerebroventricular administration, galanin-(1-16) (10 μg/15 μl) also inhibited the scopolamine (0.3 mg/kg, s.c.)-evoked release of acetylcholine, as studied in vivo by microdialysis. Substitution of [L-Trp2] for [D-Trp2] resulted in a 500-fold loss in affinity as compared with galanin-(1-16). It is concluded that, in the ventral hippocampus, the N-terminal galanin fragment [galanin-(1-16)] is recognized by the galanin receptors controlling acetylcholine release and muscarinic agonist-stimulated inositol phospholipid breakdown as a high-affinity agonist and that amino acid residue [Trp2] plays an important role in the receptor-ligand interactions.

Original languageEnglish (US)
Pages (from-to)9588-9591
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume86
Issue number23
DOIs
StatePublished - 1989
Externally publishedYes

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Galanin Receptors
Galanin
Muscarinic Agonists
endoproteinase Asp-N
Phosphatidylinositols
Hippocampus
Cholinergic Agonists
Solid-Phase Synthesis Techniques
Peptide Fragments
Scopolamine Hydrobromide
Microdialysis
Prosencephalon
Autoradiography
Inhibitory Concentration 50
Acetylcholine
Spinal Cord
Binding Sites
galanin (1-16)
Ligands
Amino Acids

Keywords

  • acetylcholine
  • muscarinic receptor
  • peptide fragments
  • release

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

N-terminal galanin-(1-16) fragment is an agonist at the hippocampal galanin receptor. / Fisone, G.; Berthold, M.; Bedecs, K.; Unden, A.; Bartfai, T.; Bertorelli, R.; Consolo, S.; Crawley, Jacqueline; Martin, B.; Nilsson, S.; Hokfelt, T.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 86, No. 23, 1989, p. 9588-9591.

Research output: Contribution to journalArticle

Fisone, G, Berthold, M, Bedecs, K, Unden, A, Bartfai, T, Bertorelli, R, Consolo, S, Crawley, J, Martin, B, Nilsson, S & Hokfelt, T 1989, 'N-terminal galanin-(1-16) fragment is an agonist at the hippocampal galanin receptor', Proceedings of the National Academy of Sciences of the United States of America, vol. 86, no. 23, pp. 9588-9591. https://doi.org/10.1073/pnas.86.23.9588
Fisone, G. ; Berthold, M. ; Bedecs, K. ; Unden, A. ; Bartfai, T. ; Bertorelli, R. ; Consolo, S. ; Crawley, Jacqueline ; Martin, B. ; Nilsson, S. ; Hokfelt, T. / N-terminal galanin-(1-16) fragment is an agonist at the hippocampal galanin receptor. In: Proceedings of the National Academy of Sciences of the United States of America. 1989 ; Vol. 86, No. 23. pp. 9588-9591.
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T1 - N-terminal galanin-(1-16) fragment is an agonist at the hippocampal galanin receptor

AU - Fisone, G.

AU - Berthold, M.

AU - Bedecs, K.

AU - Unden, A.

AU - Bartfai, T.

AU - Bertorelli, R.

AU - Consolo, S.

AU - Crawley, Jacqueline

AU - Martin, B.

AU - Nilsson, S.

AU - Hokfelt, T.

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N2 - The galanin N-terminal fragment [galanin-(1-16)] has been prepared by solid-phase synthesis and by enzymic cleavage of galanin by endoproteinase Asp-N. This peptide fragment displaced 125I-labeled galanin in receptor autoradiography experiments on rat forebrain and spinal cord and in equilibrium binding experiments from high-affinity binding sites in the ventral hippocampus with an IC50 of ~ 3 nM. In tissue slices of the same brain area, galanin-(1-16), similarly to galanin, inhibited the muscarinic agonist-stimulated breakdown of inositol phospholipids. Upon intracerebroventricular administration, galanin-(1-16) (10 μg/15 μl) also inhibited the scopolamine (0.3 mg/kg, s.c.)-evoked release of acetylcholine, as studied in vivo by microdialysis. Substitution of [L-Trp2] for [D-Trp2] resulted in a 500-fold loss in affinity as compared with galanin-(1-16). It is concluded that, in the ventral hippocampus, the N-terminal galanin fragment [galanin-(1-16)] is recognized by the galanin receptors controlling acetylcholine release and muscarinic agonist-stimulated inositol phospholipid breakdown as a high-affinity agonist and that amino acid residue [Trp2] plays an important role in the receptor-ligand interactions.

AB - The galanin N-terminal fragment [galanin-(1-16)] has been prepared by solid-phase synthesis and by enzymic cleavage of galanin by endoproteinase Asp-N. This peptide fragment displaced 125I-labeled galanin in receptor autoradiography experiments on rat forebrain and spinal cord and in equilibrium binding experiments from high-affinity binding sites in the ventral hippocampus with an IC50 of ~ 3 nM. In tissue slices of the same brain area, galanin-(1-16), similarly to galanin, inhibited the muscarinic agonist-stimulated breakdown of inositol phospholipids. Upon intracerebroventricular administration, galanin-(1-16) (10 μg/15 μl) also inhibited the scopolamine (0.3 mg/kg, s.c.)-evoked release of acetylcholine, as studied in vivo by microdialysis. Substitution of [L-Trp2] for [D-Trp2] resulted in a 500-fold loss in affinity as compared with galanin-(1-16). It is concluded that, in the ventral hippocampus, the N-terminal galanin fragment [galanin-(1-16)] is recognized by the galanin receptors controlling acetylcholine release and muscarinic agonist-stimulated inositol phospholipid breakdown as a high-affinity agonist and that amino acid residue [Trp2] plays an important role in the receptor-ligand interactions.

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