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Molecular Neurobiology

, Volume 18, Issue 2, pp 157–173 | Cite as

Glucagon-like peptide-1 (7–36) amide as a novel neuropeptide

  • Enrique Blázquez
  • Elvira Alvarez
  • Miguel Navarro
  • Isabel Roncero
  • Fernando Rodríguez-Fonseca
  • Julie A. Chowen
  • José A. Zueco
Article

Abstract

Although earlier studies indicated that GLP-1 (7–36) amide was an intestinal peptide with a potent effect on glucose-dependent insulin secretion, later on it was found that several biological effects of this peptide occur in the brain, rather than in peripheral tissues. Thus, proglucagon is expressed in pancreas, intestine, and brain, but post translational processing of the precursor yields different products in these organs, glucagon-like peptide-1 (7–36) amide being one of the forms produced in the brain. Also, GLP-1 receptor cDNA from human and rat brains has been cloned and sequenced, and the deduced amino acid sequences are the same as those found in pancreatic islets. Through these receptors, GLP-1 (7–36) amide from gut or brain sources induces its effects on the release of neurotransmitters from selective brain nuclei, the inhibition of gastric secretion and motility, the regulation of food and drink intake, thermoregulation, and arterial blood pressure. Central administration (icv) of GLP-1 (7–36) amide produces a marked reduction in food and water intake, and the colocalization of the GLP-1 receptor, GLUT-2, and glucokinase mRNAs in hypothalamic neurons involved in glucose sensing suggests that these cells may be involved in the transduction of signals needed to produce a state of fullness. In addition, GLP-1 (7–36) amide inhibits gastric acid secretion and gastric emptying, but these effects are not found in vagotomized subjects, suggesting a centrally mediated effect. Similar results have been found with the action of this peptide on arterial blood pressure and heart rate in rats. Synthesis of GLP-1 (7–36) amide and its own receptors in the brain together with its abovementioned central physiological effects imply that this peptide may be considered a neuropeptide. Also, the presence of GLP-1 (7–36) amide in the synaptosome fraction and its calcium-dependent release by potassium stimulation, suggest that the peptide may act as a neurotransmitter although further electrophysiological and ultrastructural studies are needed to confirm this possibility.

Index entries

GLP-1 (7–36) amide brain brain receptors central effects neurotransmitter release food intake water intake thermoregulation gastric acid secretion arterial blood pressure 

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Copyright information

© Humana Press Inc. 1999

Authors and Affiliations

  • Enrique Blázquez
    • 1
  • Elvira Alvarez
    • 1
  • Miguel Navarro
    • 2
  • Isabel Roncero
    • 1
  • Fernando Rodríguez-Fonseca
    • 2
  • Julie A. Chowen
    • 3
  • José A. Zueco
    • 1
  1. 1.Departamento de Bioquímica y Biología Molecular, Facultad de MedicinaUniversidad ComplutenseMadridSpain
  2. 2.Departamento de Psicobiología, Facultad de PsicologíaUniversidad ComplutenseMadridSpain
  3. 3.Instituto CajalC.S.I.C.MadridSpain

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