The effect of vasoactive intestinal polypeptide on gastric acid secretion is predominantly mediated by somatostatin.
The mechanism of action of vasoactive intestinal polypeptide on gastric acid secretion was examined in the isolated, luminally perfused mouse stomach. Vasoactive intestinal polypeptide caused a weak, transient increase in basal and histamine-stimulated acid secretion and a sustained increase in somatostatin secretion. The sustained increase in somatostatin despite return of acid to basal levels indicated that somatostatin secretion was a direct response to vasoactive intestinal polypeptide and not mediated by intraluminal acidification. The increase in somatostatin secretion was partly responsible for the weak, transient nature of the acid response since incubation with pertussis toxin, which is known to block the inhibitory effect of exogenous and endogenous somatostatin, converted the acid response to a sustained increase throughout the period of stimulation. The inhibitory influence of somatostatin was confirmed with selective vasoactive intestinal polypeptide antagonists. The antagonists inhibited vasoactive intestinal polypeptide-induced somatostatin secretion but caused a sustained increase in acid secretion. The pattern of response implied that somatostatin secretion was more sensitive than acid secretion to vasoactive intestinal polypeptide and vasoactive intestinal polypeptide antagonists and that suppression of somatostatin eliminated the main inhibitory influence on acid secretion. In addition, both vasoactive intestinal polypeptide antagonists inhibited basal somatostatin secretion, implying that input from tonically active vasoactive intestinal polypeptide neurons is responsible, at least in part, for basal somatostatin secretion.
Schubert
M L
ML
Department of Medicine, Medical College of Virginia, Richmond.
D000818:Animals; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D037342:Pertussis Toxin; D013004:Somatostatin / Q000378:metabolism / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D010566:Virulence Factors, Bordetella; D014660:Vasoactive Intestinal Peptide; D013004:Somatostatin; D006632:Histamine; D037342:Pertussis Toxin