Pentagastrin enhances gastric mucosal defenses in vivo: luminal acid-dependent and independent effects
Nishizaki, Y.; Guth, P.H.; Kim, G.; Wayland, H.; Kaunitz, J.D.
American Journal of Physiology 267(1 Pt 1): G94-104
1994
ISSN/ISBN: 0002-9513 PMID: 8048536 Document Number: 432235
Stimulation of acid secretion is associated with enhanced resistance of the gastric mucosa to damage by luminal acid. We studied the mechanism by which gastric mucosal defenses are modulated in a system in which mucus gel thickness, intracellular pH (pH-i), gastric mucosal blood flow, and acid secretion can be measured simultaneously in vivo, using a recently developed microfluorometric technique. Intravenous infusion of pentagastrin in a dose associated with maximal acid secretion increased mucus gel thickness, pH-i, and mucosal blood flow during superfusion with a neutral solution. Subsequent superfusion with an acidic buffer (pH 1.7) further increased blood flow to nearly three times basal. During superfusion with luminal acid, pH-i fell more slowly and recovered toward baseline more quickly in pentagastrin-infused rats than in controls. Pretreatment with the H-2-receptor antagonist cimetidine abolished the increased blood flow associated with pentagastrin, impairing pH-i homeostasis, although cimetidine increased mucus gel thickness in the absence of pentagastrin. We conclude that gastric defense mechanisms at the preendothelial and postepithelial levels are enhanced during acid secretion as part of a histamine-dependent homeostatic mechanism that balances gastric protective mechanisms with acid secretion. The net result of these enhanced defenses is the preservation of gastric surface cell pH-i despite the presence of a large proton gradient between lumen and blood.