Abstract
16,16-Dimethyl PGE2 (16,16-dmPGE2), given orally at 10–30 μg/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.
Similar content being viewed by others
References
Miller TA: Protective effects of prostaglandins against gastric mucosal damage: Current knowledge and proposed mechanisms. Am J Physiol 245:G601-G623, 1983
Flemström G, Garner A: Gastroduodenal HCO3 − transport: Characteristics and proposed role in acidity regulation and mucosal protection. Am J Physiol 242:G183-G193, 1982
Konturek SJ, Piastucki I, Brzozowski T: Role of prostaglandins in the formation of aspirin0induced gastric ulcers. Gastroenterology 80:4–9, 1981
Kollberg B, Aly A, Rubio C, Johansson C: Acetazolamide interferes with the protective effect of prostaglandin E2 in the rat gastric mucosa. Scand J Gastroenterol 16:385–387, 1981
Robert A, Nezamis JE, Lancaster C, Davis JP, Field SO: Antiulcer and cytoprotective effect of acetazolamide. Gastroenterology 82:1163, 1982 (abstract)
Tarnawski A, Stachura J, Mach T, Terano A, Ivey KJ: Role of carbonic anhydrase in prostaglandin protection of rat gastric mucosa against ethanol. Gastroenterology 82:1193, 1982 (abstract)
Reichstein BJ, Cohen MM: Effect of acetazolamide on prostaglandin cytoprotection of the rat stomach. Surg Forum 33:171–172, 1982
Konturek SJ, Brzozowski T, Piastucki I, Radecki T: Gastric cytoprotection by acetazolamide: Role of endogenous prostaglandins. Digestion 28:125–131, 1983
Bradford M: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein dye binding. Anal Biochem 72:248–254, 1976
Zade-Oppen AMM: A method for the determination of hemoglobin in dilute solutions. Acta Soc Med Ups 65: 249–257, 1960
Maren TH: A simplified micromethod for the determination of carbonic anhydrase and its inhibitors. J Pharmacol Exp Ther 130:26–29, 1960
Okabe S, Ohtsu K, Takeuchi K, Takagi K: Effect ofl-glutamine on indomethacin0induced gastric lesions in the rat. Jpn J Pharmacol 24:169–171, 1974
Takagi K, Okabe S: The effects of drugs on the production and recovery processes of the stress ulcer. Jpn J Pharmacol 18:9–18, 1968
Takagi K, Kasuya Y, Watanabe K: Studies on the drugs for peptic ulcer. A reliable method for producing stress ulcer in rats. Chem Pharm Bull 12:465–472, 1964
Okabe S, Ishihara Y, Inoo H, Tanaka H: Mepirizole-induced duodenal ulcers in rats and their pathogenesis. Dig Dis Sci 27:242–249, 1982
Ohtsuki H, Takeuchi K, Okabe S: Effects of 16,16-dimethyl prostaglandin E2 on morphological and functional alteration of the rat gastric mucosa induced by ethanol. Gastroenterology 86:1200, 1984 (abstract)
Ohno T, Ohtsuki H, Okabe S: Effects of 16,16-dimethyl PGE2 on ethanol-and aspirin-induced gastric damage in the rat. Scanning electron microscopic study. Gastroenterology 88:353–361, 1985
Bolton JP, Cohen MM: Stimulation of non-parietal cell secretion in canine Heidenhain pouches by 16,16-dimethyl prostaglandin E2. Digestion 17:291–299, 1978
Bolton JP, Cohen MM: Effect of 16,16-dimethyl prostaglandin E2 on the gastric mucosal barrier. Gut 20:513–517, 1979
Kitagawa H, Fujiwara M, Osumi T: Effects of water-immersion stress on gastric secretion and mucosal blood flow in rats. Gastroenterology 77:298–302, 1979
Basso N, Materia A, Forlini A, Jaffe BM: Prostaglandin generation in the gastric mucosa of rats with stress ulcer. Surgery 94:104–108, 1983
Larsen KR, Moody FG: 16,16-Dimethyl PGE2 and HCO3 − efflux. Dig Dis Sci 28:649–650, 1983
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Takeuchi, K., Ohtsuki, H. & Okabe, S. Mechanisms of protective activity of 16,16-dimethyl PGE2 and acetazolamide on gastric and duodenal lesions in rats. Digest Dis Sci 31, 406–411 (1986). https://doi.org/10.1007/BF01311677
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01311677