The hepatic vagal reception of intraportal GLP-1 is via receptor different from the pancreatic GLP-1 receptor

J Auton Nerv Syst. 2000 Apr 12;80(1-2):14-21. doi: 10.1016/s0165-1838(99)00086-7.

Abstract

Glucagon-like peptide-1 (7-36)amide (tGLP-1), a representative humoral incretin, released into the portal circulation in response to a meal ingestion, exerts insulinotropic action through binding to the tGLP-1 receptor known to be a single molecular form thus far. We previously reported that the hepatic vagal nerve is receptive to intraportal tGLP-1, but not to non-insulinotropic full-length GLP-1-(1-37), through a mechanism mediated by specific receptor to the hormone. In the present study, we aimed to examine how modification of the receptor function alters this neural reception of tGLP-1, by using the specific agonist, exendin-4, and the specific antagonist, exendin (9-39)amide, of the receptor at doses known to exert their effects on the insulinotropic action of tGLP-1. Intraportal injection of 0.2 or 4.0 pmol tGLP-1, a periphysiological and pharmacological dose, respectively, facilitated significantly the afferent impulse discharge rate of the hepatic vagus in anesthetized rats, as reported previously. However, unexpectedly, intraportal injection of exendin-4 at a dose of 0.2 or 4.0 pmol, or of even 40.0 pmol, did not facilitate the afferents at all. Moreover, intraportal injection of exendin (9-39)amide at 100 times or more molar dose to that of tGLP-1, either 5 min before or 10 min after injection of 0.2 or 4.0 pmol tGLP-1, failed to modify the tGLP-1-induced facilitation of the afferents. The present results suggest that the neural reception of tGLP-1 involves a receptor mechanism distinct from that in the well-known humoral insulinotropic action.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Electrophysiology
  • Exenatide
  • Glucagon
  • Glucagon-Like Peptide 1
  • Glucagon-Like Peptide-1 Receptor
  • Glucagon-Like Peptides
  • Injections, Intravenous
  • Liver / innervation*
  • Male
  • Neurons, Afferent / chemistry
  • Neurons, Afferent / drug effects
  • Neurons, Afferent / physiology
  • Pancreas / chemistry*
  • Peptide Fragments / pharmacokinetics*
  • Peptide Fragments / pharmacology
  • Peptides / pharmacology
  • Portal Vein
  • Rats
  • Rats, Wistar
  • Receptors, Glucagon / analysis*
  • Vagus Nerve / chemistry*
  • Vagus Nerve / cytology
  • Vagus Nerve / physiology
  • Venoms*

Substances

  • Glp1r protein, rat
  • Glucagon-Like Peptide-1 Receptor
  • Peptide Fragments
  • Peptides
  • Receptors, Glucagon
  • Venoms
  • glucagon-like peptide 1 (7-36)amide
  • exendin (9-39)
  • Glucagon-Like Peptides
  • Glucagon-Like Peptide 1
  • Glucagon
  • Exenatide