Effects of cimetidine administered in cytoprotective and antisecretory doses on the membrane-bound ATP-dependent energy systems in the gastric mucosal lesions induced by HCl in rats.
CFY strain rats (both sexes, 180-210 g) were fasted for 24 hr. Different doses of cimetidine (2.5, 10 and 50 mg X kg-1 i.p.) were given 30 min prior to the gastric mucosal lesions induced by the intragastric application of 0.6 M HCl. Animals were sacrificed 1 hr after the administration of the necrotizing agent. The number of gastric lesions was determined and their severity scored. Samples from the gastric fundic mucosa were taken for biochemical analysis. The tissue levels of adenosine-5'-triphosphate (ATP), adenosine-5'-diphosphate (ADP), adenosine-5'-monophosphate (AMP) and L-(+)-lactate were determined enzymatically, while the tissue contents of cyclic 3',5' adenosine monophosphate were measured by radioimmunoassay. The values for adenylate pool (ATP + ADP + AMP)-1 were calculated. All biochemical results were computed for 1.0 mg mucosal protein. We found that (1) the levels of ADP and lactate rose significantly, while ATP, AMP, cAMP, ATP X ADP-1 and energy charge decreased during the development of gastric lesions induced by HCl: (2) cimetidine decreased dose-dependently the number and severity of lesions: (3) the levels of ATP, ADP X ADP-1, and energy charge were increased dose-dependently by cimetidine, while AMP and lactate were decreased: (4) the levels of ADP, adenylate pool and cAMP did not change significantly by cimetidine.(ABSTRACT TRUNCATED AT 250 WORDS)
D000244:Adenosine Diphosphate / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects; D002927:Cimetidine / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects*; D006851:Hydrochloric Acid / Q000633:toxicity*; D008297:Male; D051381:Rats; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000517:prevention & control
D000244:Adenosine Diphosphate; D002927:Cimetidine; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D000251:Adenosine Triphosphatases; D000262:Adenylyl Cyclases; D006851:Hydrochloric Acid