TRH-induced vagal stimulation of duodenal HCO-3 mediated by VIP and muscarinic pathways.
The central nervous system effects of thyrotropin-releasing hormone (TRH) on proximal duodenal bicarbonate secretion were studied in freely moving rats. Cerebroventricular administration of TRH (0.5-5.0 nmol) significantly stimulated basal duodenal bicarbonate secretion, whereas intravenous administration of TRH did not. Ganglionic blockade with chlorisondamine and truncal vagotomy abolished TRH-induced bicarbonate secretion, whereas atropine significantly attenuated the response. The vasoactive intestinal peptide (VIP) receptor antagonist, (4Cl-D-Phe6, Leu17) VIP given intravenously completely prevented the stimulatory effect of central TRH on duodenal bicarbonate secretion. In contrast, hypophysectomy, adrenalectomy, opiate and noradrenergic blockade, or indomethacin did not affect the TRH-induced bicarbonate response. Intravenous administration of VIP and carbachol significantly stimulated bicarbonate outputs, and these responses were blocked by the VIP antagonist and atropine, respectively. These results indicate that TRH may serve as a central nervous system mediator that stimulates duodenal bicarbonate secretion in rats by increasing vagal outflow. Vagal stimulation induced by TRH increases duodenal bicarbonate secretion by the release of VIP and, in part, by activation of a muscarinic pathway but not by pituitary, adrenal, and noradrenergic pathways or endogenous opiates and prostaglandins. The actions of peripheral VIP and carbachol appear to be mediated by specific VIP and muscarinic receptors, respectively.
Lenz
H J
HJ
Department of Medicine, University of Hamburg, Federal Republic of Germany.
Vale
W W
WW
Rivier
J E
JE
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001639:Bicarbonates / Q000378:metabolism*; D001921:Brain / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D002714:Chlorisondamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000378:metabolism*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D009116:Muscarine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009496:Neurotensin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*; D014630:Vagus Nerve / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D001615:beta-Endorphin / Q000494:pharmacology
D001639:Bicarbonates; C048507:vasoactive intestinal peptide, 4-chloro-Phe(6)-Leu(17)-; D014660:Vasoactive Intestinal Peptide; D009496:Neurotensin; D013973:Thyrotropin-Releasing Hormone; D001615:beta-Endorphin; D001285:Atropine; D009116:Muscarine; D002217:Carbachol; D002714:Chlorisondamine