Mechanisms of protective activity of 16,16-dimethyl PGE2 and acetazolamide on gastric and duodenal lesions in rats.
16,16-Dimethyl PGE2 (16,16-dmPGE2), given orally at 10-30 micrograms/kg, had no effects on gastric acid secretion, or carbonic anhydrase activity, but did increase HCO3- secretion in both the stomach and duodenum of rats. 16,16-dmPGE2, at nonantisecretory doses, potently inhibited indomethacin- and water-immersion stress-induced gastric lesions and mepirizole-induced duodenal lesions in rats. Acetazolamide, given orally at 50 mg/kg, markedly inhibited carbonic anhydrase activity, but had no effects on gastric acid secretion and the basal and 16,16-dmPGE2-stimulated HCO3- secretion. Acetazolamide, at a nonantisecretory dose, had no effects on indomethacin-induced gastric lesions and mepirizole-induced duodenal lesions, but significantly inhibited water-immersion stress-induced gastric lesions. Combined administration of 16,16-dmPGE2 and acetazolamide did not influence the protective activity of 16,16-dmPGE2 on these lesions. The mechanism of the cytoprotective activity of 16,16-dmPGE2 may involve an increase in HCO3- secretion (nonmediated by carbonic anhydrase), while mechanisms involved in the effects of acetazolamide are apparently different.
Takeuchi
K
K
Ohtsuki
H
H
Okabe
S
S
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology*; D000086:Acetazolamide / Q000494:pharmacology*; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D002256:Carbonic Anhydrases / Q000378:metabolism; D004386:Duodenum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004840:Epirizole / Q000037:antagonists & inhibitors; D005750:Gastric Juice / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007101:Immersion; D007213:Indomethacin / Q000037:antagonists & inhibitors; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013312:Stress, Physiological / Q000473:pathology
D001639:Bicarbonates; D011459:Prostaglandins E, Synthetic; D004840:Epirizole; D002256:Carbonic Anhydrases; D015064:16,16-Dimethylprostaglandin E2; D000086:Acetazolamide; D007213:Indomethacin