A pharmacological approach to cellular mechanisms of PGI2-induced gastric cytoprotection on ethanol-induced gastric mucosal damage in rats.
The aims of this study were as follows: 1. to analyse the effects of drugs with different subcellular mechanisms on the PGI2-induced gastric cytoprotection in a non acid dependent (ethanol-induced) gastric ulcer model; 2. to identify the affinity and intrinsic activity curves on the PGI2-induced gastric cytoprotection; 3. to evaluate the main cellular mechanisms of PGI2-induced gastric mucosal defence. The observations were carried out on both sexes of CFY-strain rats, weighing 180 to 210 g. The gastric mucosal damage was produced by intragastric administration of 96% ethanol. The animals were killed at 1 hr after administration of ethanol, and the number and severity of gastric mucosal lesions (ulcers) was noted. Atropine, actinomycin D, cimetidine, mannomustine, dinitrophenol, epinephrine, pentagastrin, histamine, ouabain, tetracycline were given intraperitoneally (in different doses) at 30 min before administration of ethanol. The effects of these drugs were tested on the PGI2-induced (5 micrograms/kg was given intragastrically) gastric cytoprotection. It has been found that: 1. atropine, actinomycin D, cimetidine, epinephrine, ouabain, tetracycline and mannomustine inhibited the PGI2-induced gastric cytoprotection; 2. histamine, pentagastrin and 2,4-dinitrophenol enhanced the PGI2-induced gastric cytoprotection; 3. the molar concentrations of these drugs modifying the PGI2-induced gastric cytoprotection differed significantly. It has been concluded that: 1. the drugs stimulating or inhibiting the cell functions are capable to modify the extent of PGI2-induced gastric cytoprotection; 2. different subcellular mechanisms (oxidative phosphorylation, increased synthesis of proteins, ribonucleic and deoxyribonucleic acids, modifications of membrane-bound ATP-dependent energy systems) are involved in the development of PGI2-induced gastric cytoprotection.
Mózsik
G
G
First Department of Medicine, Medical University of Pécs, Hungary.
Garamszegi
M
M
Jávor
T
T
Nagy
L
L
Sütö
G
G
Vincze
A
A
D000818:Animals; D004357:Drug Synergism; D011464:Epoprostenol / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D000431:Ethanol / Q000037:antagonists & inhibitors; D005260:Female; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control*
D000431:Ethanol; D011464:Epoprostenol