Prevention of phenylbutazone ulcer in the rat by glucose: role of a glycoprivic receptor system

Abstract

The mechanism by which the extra gastric administration of phenylbutazone (PBZ) and by which other nonsteroid antiinflammatory drugs induce a vagally mediated gastric hypercontractile response and ulceration is unknown. Glucose administration protects the rat and the monkey from the ulcerogenic action of aspirin. By uncoupling oxidative phosphorylation PBZ might stimulate an energy-sensitive receptor system that results in the gastric contractile response. Glucose feeding or i.v. infusion prevented or abolished the gastric contractile response to the intraileal injection of 22.5 mg PBZ in cervical-sectioned rats with miniature gastric balloons. Glucose treatment also significantly reduced ulceration and hemorrhage. Fructose infusion was less effective. Mannitol infusion had no effect on the PBZ-induced gastric contractile activity, and all animals developed severe ulceration and hemorrhage. Blood glucose levels fell significantly in starved rats treated with PBZ. Glucose feeding and glucose or fructose infusion prevented or reduced this effect. Evidently, alleviating the glucoprivic state induced by PBZ glucose abolishes the gastric contractile response and prevents ulceration and hemorrhage.