Glucagon-like peptide 1 (7-36) amide (GLP-1) and exendin-4 stimulate serotonin release in rat hypothalamus

Peptides. 2008 Aug;29(8):1377-81. doi: 10.1016/j.peptides.2008.04.007. Epub 2008 Apr 20.

Abstract

Glucagon-like peptide 1 (7-36) amide (GLP-1) and exendin-4 are gastrointestinal hormones as well as neuropeptides involved in glucose homeostasis and feeding regulation, both peripherally and at the central nervous system (CNS), acting through the same GLP-1 receptor. Aminergic neurotransmitters play a role in the modulation of feeding in the hypothalamus and we have previously found that peripheral hormones and neuropeptides, which are known to modulate feeding in the central nervous system, are able to modify catecholamine and serotonin release in the hypothalamus. In the present paper we have evaluated the effects of GLP-1 and exendin-4 on dopamine, norepinephrine, and serotonin release from rat hypothalamic synaptosomes, in vitro. We found that glucagon-like peptide 1 (7-36) amide and exendin-4 did not modify either basal or depolarization-induced dopamine and norepinephrine release; on the other hand glucagon-like peptide 1 (7-36) amide and exendin-4 stimulated serotonin release, in a dose dependent manner. We can conclude that the central anorectic effects of GLP-1 agonists could be partially mediated by increased serotonin release in the hypothalamus, leaving the catecholamine release unaffected.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dopamine / metabolism
  • Exenatide
  • Glucagon-Like Peptide 1 / pharmacology
  • Glucagon-Like Peptide 1 / physiology*
  • Hypoglycemic Agents / metabolism
  • Hypothalamus / chemistry*
  • Male
  • Norepinephrine / metabolism
  • Peptide Fragments / pharmacology
  • Peptide Fragments / physiology*
  • Peptides / pharmacology
  • Peptides / physiology*
  • Rats
  • Rats, Wistar
  • Serotonin / metabolism*
  • Synaptosomes / chemistry
  • Synaptosomes / drug effects*
  • Synaptosomes / metabolism
  • Venoms / pharmacology

Substances

  • Hypoglycemic Agents
  • Peptide Fragments
  • Peptides
  • Venoms
  • glucagon-like peptide 1 (7-36)amide
  • Serotonin
  • Glucagon-Like Peptide 1
  • Exenatide
  • Dopamine
  • Norepinephrine