Membrane-bound ATP-dependent energy systems and gastric cytoprotection by prostacyclin, atropine and cimetidine in the rat.
The effects were studied of different doses of prostacyclin (PG12), atropine and cimetidine on the gastric secretory responses of four-hour pylorus-ligated rats and on the gastric mucosal damage produced by intragastric administration of 0.6 M HCl, to determine the cytoprotective doses of PG12, atropine and cimetidine. In another series of observations, gastric mucosal damage was produced by intragastric administration of 0.6 M HCl and the effects were studied of cytoprotective doses of PG12, atropine and cimetidine on the number and severity of gastric lesions, in connection with the biochemical changes of the rat gastric fundic mucosa. The drugs were given intraperitoneally 30 min before the application of the necrotizing agent, and the animals were killed one hour later. During the experiments, the tissue levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and lactate were measured enzymatically, and the tissue content of cyclic adenosine monophosphate (cAMP) was determined by radioimmunoassay. The specimens were taken from the gastric fundic mucosa of groups of animals treated with saline solution (absolute control), with 0.6 M HCl (pathological control) and with 0.6 M HCl plus PG12, atropine and cimetidine (given in cytoprotective doses). The ratio of ATP.ADP-1, adenylate pool (ATP + ADP + AMP) and energy charge (ATP + 0.5 ADP.ATP + ADP + AMP-1) were calculated in all groups of animals. It was found that: (i) PG12 (in a dose of 5 micrograms.kg-1) atropine (in a dose of 0.025 mg.kg-1) and cimetidine (in a dose of 2.5 micrograms.kg-1) have cytoprotective effects; (ii) the gastric fundic mucosal damage produced by intragastric administration of 0.6 M HCl appears as a result of a positive metabolic adaptation of the gastric fundic mucosa; (iii) the development of gastric cytoprotection by PG12, atropine and cimetidine give rise to very different changes in the tissue levels of ATP, ADP, AMP and cAMP.(ABSTRACT TRUNCATED AT 400 WORDS)
D000109:Acetylcholine / Q000494:pharmacology; D000227:Adenine Nucleotides / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D002927:Cimetidine / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology*; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D005755:Gastrins / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D006851:Hydrochloric Acid / Q000494:pharmacology; D007773:Lactates / Q000378:metabolism; D008297:Male; D010276:Parasympatholytics / Q000494:pharmacology; D051381:Rats
D000227:Adenine Nucleotides; D005755:Gastrins; D007773:Lactates; D010276:Parasympatholytics; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D001285:Atropine; D002927:Cimetidine; D006632:Histamine; D000255:Adenosine Triphosphate; D011464:Epoprostenol; D000242:Cyclic AMP; D000251:Adenosine Triphosphatases; D000262:Adenylyl Cyclases; D000109:Acetylcholine; D006851:Hydrochloric Acid; D004837:Epinephrine