Pathogenesis of compound 48/80-induced gastric lesions in rats.
Intraperitoneal administration of 0.75 mg/kg of compound 48/80 (a mast cell degranulator) once daily for four days induced extensive gastric lesions in rats. Oral administration of tripelennamine (histamine H1-receptor antagonist) and cimetidine (histamine H2-receptor antagonist) twice daily for four days had little or no effect on the lesion formation. Oral administration of methysergide and cyproheptadine (serotonin antagonists) and FPL-52694 (a mast cell stabilizer) potently inhibited the compound 48/80-induced lesions. Intraperitoneal administration of histamine plus serotonin, or serotonin alone, induced gastric lesions which resembled those induced by compound 48/80. These lesions were potently inhibited by methysergide and cyproheptadine, but not by tripelennamine, cimetidine, and FPL-52694. Single or repeated administration of compound 48/80 significantly increased serum histamine and serotonin levels. After a single administration of compound 48/80, the increased histamine levels rapidly returned to normal levels, but serotonin levels remained high for 7 hr. Histamine and serotonin levels in the gastric mucosa were transiently increased after a single administration of compound 48/80, but remained normal after repeated administration. Single or repeated administration of compound 48/80 had little effect on arterial blood pressure. The compound 48/80-induced gastric lesions appear to be caused primarily by the release of serotonin, but not histamine, from extragastric sources.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D003533:Cyproheptadine / Q000494:pharmacology; D004347:Drug Interactions; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006632:Histamine / Q000097:blood / Q000378:metabolism / Q000633:toxicity; D008297:Male; D008407:Mast Cells / Q000187:drug effects; D008784:Methysergide / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000097:blood / Q000378:metabolism / Q000633:toxicity; D013272:Stomach Diseases / Q000139:chemically induced* / Q000473:pathology; D014309:Tripelennamine / Q000494:pharmacology; D003189:p-Methoxy-N-methylphenethylamine / Q000633:toxicity*
D002867:Chromones; D003533:Cyproheptadine; D012701:Serotonin; D014309:Tripelennamine; D003189:p-Methoxy-N-methylphenethylamine; C029061:FPL-52694; D002927:Cimetidine; D006632:Histamine; D008784:Methysergide