Cellular mechanisms of the development of gastric mucosal damage and of gastrocytoprotection induced by prostacyclin in rats. A pharmacological study

Abstract

The rat gastric mucosal damage (lesion) can be produced by the topical application of 96% ethanol and its development can be prevented by the administration of prostacyclin (PGI2) in doses which have no inhibitory effect on gastric acid secretion. The bases for this phenomenon are unknown. In this study the following observations were carried out: 1. The effects of different drugs (actinomycin D, atropine, cimetidine, Degranol,2,4-dinitro-phenol, histamine, epinephrine, pentagastrin, prostacyclin, tetracycline) and of bilateral surgical vagotomy were studied on the development of ethanol-induced rat gastric mucosal damage (ulcer); 2. The effect of PGI2 (applied in a dose of 5 μg/kg) was studied on the ulcer preventive effects of different drugs and of surgical vagotomy; 3. The effects of different drugs and of surgical vagotomy were estimated on the development of gastrocytoprotection produced by PGI2. The drugs and surgical vagotomy were applied alone or in a parallel administration with the PGI2 cytoprotective dose of μg/kg, at 30 minutes before giving the ethanol. The animals were killed 1 hr after ethanol administration. The number of gastric lesions (ulcers) were noted and their severities scored. The single application of atropine, cimetidine, Degranol, epinephrine, histamine, pentagastrin and PGI2 decreased significantly the number and severity of ulcers; the other drugs (tetracycline, actinomycin D,2,4-dinitrophenol) diminished the lesions but without statistical significance. The PGI2 ( in a dose of 5 μg/kg) decreased significantly the ulcer preventive effect of Degranol, tetracycline, cimetidine, atropine, epinephrine and of surgical vagotomy; while the effects of actinomycin D, pentagastrin and 2,4-dinitrophenol were significantly increased by PGI2 administration. The cytoprotective effect of PGI2 was decreased significantly when it was given together with Degranol, tetracycline, actinomycin D, cimetidine, atropine, epinephrine and surgical vagotomy. The parallel administration of PGI2 with pentagastrin and 2,4-dinitrophenol increased significantly the extent of PGI2-induced gastrocytoprotection. These data suggest that very complex cellular mechanisms (energy liberations, d e n o v o synthesis of DNA,RNA,protein, oxydative phosphorylation) may be involved in the development of gastric mucosal damage by topical application of ethanol and of gastrocytoprotection produced by PGI2.