Prevention of phenylbutazone ulcer in the rat by glucose: role of a glycoprivic receptor system.
The mechanism by which the extragastric administration of phenylbutazone (PBZ) and other nonsteroid anti-inflammatory drugs induce a vagally mediated gastric hypercontractile response and ulceration is unknown. Glucose administration has been reported to protect the rat and the monkey from the ulcerogenic action of aspirin. It was postulated that by uncoupling oxidative phosphorylation PBZ might stimulate an energy-sensitive receptor system that results in the gastric contractile response. Glucose feeding or intravenous infusion was seen to prevent or abolish the gastric contractile response to the intraileal injection of 22.5 mg of PBZ in cervical-sectioned rats with miniature gastric balloons. Glucose treatment also significantly reduced ulceration and hemorrhage. Fructose infusion was somewhat 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. It is suggested that by alleviating the "glucoprivic state" induced by PBZ glucose abolishes the gastric contractile response and prevents ulceration and hemorrhage.
D000818:Animals; D005260:Female; D005632:Fructose / Q000494:pharmacology; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000517:prevention & control; D005947:Glucose / Q000494:pharmacology / Q000627:therapeutic use*; D008353:Mannitol / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D010653:Phenylbutazone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000502:physiology*; D013270:Stomach / Q000502:physiology; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control*
D011956:Receptors, Cell Surface; C027786:glucose receptor; D005632:Fructose; D008353:Mannitol; D010653:Phenylbutazone; D005947:Glucose