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Research ArticleCELLULAR AND MOLECULAR

SLC-1 Receptor Mediates Effect of Melanin-Concentrating Hormone on Feeding Behavior in Rat: A Structure-Activity Study

Thomas Suply, Odile Della Zuana, Valérie Audinot, Marianne Rodriguez, Philippe Beauverger, Jacques Duhault, Emmanuel Canet, Jean-Pierre Galizzi, Jean-Louis Nahon, Nigel Levens and Jean A. Boutin
Journal of Pharmacology and Experimental Therapeutics October 2001, 299 (1) 137-146;
Thomas Suply
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Odile Della Zuana
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Valérie Audinot
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Marianne Rodriguez
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Philippe Beauverger
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Jacques Duhault
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Emmanuel Canet
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Jean-Pierre Galizzi
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Jean-Louis Nahon
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Nigel Levens
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Jean A. Boutin
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Abstract

Several studies have shown that melanin-concentrating hormone (MCH) is an orexigenic peptide in rat. In the present study, a structure-activity relationship with MCH analogs was performed in rat, both in vitro and in vivo. On rat recombinant SLC-1 receptor, both cAMP inhibition and [125I]S36057 binding were measured. In vivo, these analogs were injected intracerebroventricularly in rats and their effects were evaluated upon food intake. First, data obtained with the rat recombinant receptor were highly correlated with those obtained from its human counterpart. Second, agonist potencies in the cAMP assay were also highly correlated with binding affinities. These peptides could be classified into several groups according to their potency at the SLC-1 receptor (from subnanomolar activity to complete inactivity). Indeed, there was a strong correlation between their effects upon food intake and the results obtained at the rat SLC-1 receptor. The present report describes for the first time the rat SLC-1 receptor pharmacology and clearly establishes the relevance of the SLC-1 receptor in feeding behavior.

Footnotes

  • T.S. was a recipient of a Convention CIFRE between the Association Nationale de la Recherche Technique, the Institut de Recherche SERVIER, and the Center National de la Recherche Scientifique.

  • Abbreviations:
    MCH
    melanin-concentrating hormone
    PCR
    polymerase chain reaction
    HEK
    human embryonic kidney
    CSF
    cerebrospinal fluid
    RT-PCR
    reverse transcription-polymerase chain reaction
    ANOVA
    analysis of variance
    • Received March 29, 2001.
    • Accepted June 4, 2001.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 299 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 299, Issue 1
1 Oct 2001
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Research ArticleCELLULAR AND MOLECULAR

SLC-1 Receptor Mediates Effect of Melanin-Concentrating Hormone on Feeding Behavior in Rat: A Structure-Activity Study

Thomas Suply, Odile Della Zuana, Valérie Audinot, Marianne Rodriguez, Philippe Beauverger, Jacques Duhault, Emmanuel Canet, Jean-Pierre Galizzi, Jean-Louis Nahon, Nigel Levens and Jean A. Boutin
Journal of Pharmacology and Experimental Therapeutics October 1, 2001, 299 (1) 137-146;

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Research ArticleCELLULAR AND MOLECULAR

SLC-1 Receptor Mediates Effect of Melanin-Concentrating Hormone on Feeding Behavior in Rat: A Structure-Activity Study

Thomas Suply, Odile Della Zuana, Valérie Audinot, Marianne Rodriguez, Philippe Beauverger, Jacques Duhault, Emmanuel Canet, Jean-Pierre Galizzi, Jean-Louis Nahon, Nigel Levens and Jean A. Boutin
Journal of Pharmacology and Experimental Therapeutics October 1, 2001, 299 (1) 137-146;
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