title: Effect of verapamil on the gastric mucosal level of PGE2 during stress.
abstract: Prostaglandin E2 is one of the factors in the maintenance of gastric mucosal integrity and verapamil, a calcium channel blocker, has been shown to reduce gastric mucosal ulcerations during stress. To investigate whether this protective effect of verapamil is mediated via PGE2, four groups of 20 Holtzman rats were given either 1 ml of normal saline (NS) intraperitoneally (ip): 1 mg/kg of indomethacin (I) ip; 2 mg/kg of verapamil (V) ip or I followed by V. Then 10 animals from each group were submitted to stress by the cold-restraint method. After sacrifice, gastric mucosal ulcerations were counted and specimens of nonulcerated mucosa were assayed for PGE2 by HPLC. Stress-induced mucosal ulcerations were associated with a significant decrease in the gastric mucosal levels of PGE2 (from 64.2 to 32.7 pg; P less than 0.05). This effect was magnified by the administration of indomethacin (down to 21.0 pg). Verapamil significantly increased PGE2 levels both in the stressed (48.0 pg) and unstressed (99.9 pg) animals and significantly reduced ulcerogenesis when compared to either NS- or I-treated groups. This effect of verapamil was completely blocked by the administration of indomethacin. In conclusion, verapamil stimulates PGE2 synthesis and its protective effect against stress-induced mucosal damage seems to be mediated by PGE2.
authors.affiliation: Department of Surgery, Long Island Jewish Medical Center, New Hyde Park, New York 11042.
authors.forename: L J
authors.initials: LJ
authors.lastname: Auguste
authors.forename: H R
authors.initials: HR
authors.lastname: Sterman
authors.forename: T A
authors.initials: TA
authors.lastname: Stein
authors.forename: B
authors.initials: B
authors.lastname: Bailey
authors.forename: L
authors.initials: L
authors.lastname: Wise
mesh_terms: D000818:Animals; D015232:Dinoprostone / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D013312:Stress, Physiological / Q000378:metabolism* / Q000517:prevention & control; D014700:Verapamil / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D014700:Verapamil; D015232:Dinoprostone