Pentagastrin enhances gastric mucosal defenses in vivo: luminal acid-dependent and independent effects.
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 (pHi), 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, pHi, 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, pHi fell more slowly and recovered toward baseline more quickly in pentagastrin-infused rats than in controls. Pretreatment with the H2-receptor antagonist cimetidine abolished the increased blood flow associated with pentagastrin, impairing pHi 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 pHi despite the presence of a large proton gradient between lumen and blood.
Nishizaki
Y
Y
Medical Service, Wadsworth Veterans Affairs Medical Center, Los Angeles 90073.
Guth
P H
PH
Kim
G
G
Wayland
H
H
Kaunitz
J D
JD
D000818:Animals; D005744:Gastric Acid / Q000502:physiology*; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D008297:Male; D009093:Mucus / Q000737:chemistry; D010418:Pentagastrin / Q000494:pharmacology*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects
D010418:Pentagastrin