title: Inhibitory effect of DS-4574, a peptidoleukotriene antagonist with mast cell stabilizing action, on compound 48/80-induced gastric mucosal lesions in rats.
abstract: We evaluated the inhibitory effect of DS-4574, a peptidoleukotriene antagonist with mast cell stabilizing action, on rat gastric mucosal lesions induced by compound 48/80 (C48/80: a mast cell degranulator), in comparison with those of disodium cromoglycate (DSCG: a mast cell stabilizer), LY171883 (a peptidoleukotriene antagonist) and cimetidine (a histamine H2 receptor antagonist). Subcutaneous administration of C48/80 (1 mg/kg) once daily for four consecutive days produced extensive gastric lesions in the fundic mucosa. DS-4574 (20, 50 and 100 mg/kg/day, oral) and DSCG (200 mg/kg/day, intraperitoneal) treatment markedly inhibited formation of these mucosal lesions, but LY171883 (100 and 200 mg/kg/day, oral) and cimetidine (400 mg/kg/day, oral) treatment did not. Moreover, DS-4574 and DSCG significantly suppressed both hyperhistaminemia and histamine release from rat peritoneal mast cells induced by C48/80. These results indicate that the inhibitory effect of DS-4574 on gastric lesions induced by C48/80 may be related to its mast cell stabilizing action, but to neither its antisecretory nor its peptidoleukotriene antagonistic activity.
authors.affiliation: Exploratory Research Laboratories III, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tabuchi
authors.forename: K
authors.initials: K
authors.lastname: Kawarabayashi
authors.forename: K
authors.initials: K
authors.lastname: Furuhama
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D002927:Cimetidine / Q000494:pharmacology; D004205:Cromolyn Sodium / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects*; D006632:Histamine / Q000097:blood; D006636:Histamine Release / Q000187:drug effects; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D020024:Leukotriene Antagonists; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology*; D003189:p-Methoxy-N-methylphenethylamine / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000098:Acetophenones; D020024:Leukotriene Antagonists; D011743:Pyrimidines; D013777:Tetrazoles; D014230:Triazoles; C076052:DS 4574; D003189:p-Methoxy-N-methylphenethylamine; D002927:Cimetidine; D006632:Histamine; C044660:LY 171883; D004205:Cromolyn Sodium