The hepatic vagal reception of intraportal GLP-1 is via receptor different from the pancreatic GLP-1 receptor.
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.
Nishizawa
M
M
Division of Life Science, Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa, Japan.
Nakabayashi
H
H
Kawai
K
K
Ito
T
T
Kawakami
S
S
Nakagawa
A
A
Niijima
A
A
Uchida
K
K
D000818:Animals; D004594:Electrophysiology; D000077270:Exenatide; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D004763:Glucagon-Like Peptides; D007275:Injections, Intravenous; D008099:Liver / Q000294:innervation*; D008297:Male; D009475:Neurons, Afferent / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D010179:Pancreas / Q000737:chemistry*; D010446:Peptide Fragments / Q000493:pharmacokinetics* / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D011169:Portal Vein; D051381:Rats; D017208:Rats, Wistar; D018027:Receptors, Glucagon / Q000032:analysis*; D014630:Vagus Nerve / Q000737:chemistry* / Q000166:cytology / Q000502:physiology; D014688:Venoms
C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D010446:Peptide Fragments; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; C055453:glucagon-like peptide 1 (7-36)amide; C083773:exendin (9-39); D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D000077270:Exenatide