Gastrointestinal ulceration in the guinea pig in response to dimaprit, histamine, and H1- and H2-blocking agents

Abstract

Histamine is known to induce gastric ulcers in guinea pigs after intraperitoneal administration and duodenal ulcers after repeated intramuscular administrations. This study was undertaken to clarify further the differential role of H1 and H2 receptor sites in respect to gastric and duodenal ulcer in the guinea pig. Groups of guinea pigs were treated with histamine, intraperitoneal (1.81 mg/kg intraperitoneal) or intramuscular (0.09 mg/kg intramuscular X 8 doses); the selective H2 agonist dimaprit (0.09-0.18 mg/kg X 8 doses intramuscular or 1.81-3.62 mg/kg intraperitoneal); NaCl, 154 mM (control); and the selective H1 and H2 antagonists, diphenhydramine (125 mg/kg X 2 doses, intramuscular) or cimetidine (50 mg/kg X 3 doses, intramuscular). Gastric and duodenal lesions were evaluated and residual gastric contents were analyzed. The selective induction of gastric or duodenal ulceration by histamine was confirmed, and the H2 agonist, dimaprit, has been shown to be ulcerogenic to the guinea pig duodenum by intraperitoneal or intramuscular administration. Diphenhydramine produced considerably more protection against histamine-induced gastric ulceration (62% decrease in incidence), while cimetidine was particularly effective in the prevention of histamine-induced duodenal ulcer (64% decrease in incidence). A differential role of histamine in the pathogenesis of gastric as opposed to duodenal ulcer is suggested by the present findings.