Abstract
The effects of U-46619, a stable analogue of the prostaglandin endoperoxide PGH2, were studied on canine gastric acid secretion, gastric mucosal blood flow, and secretion of mucus into gastric juice and compared to those of PGE2. U-46619 was approximately four and three times as potent as PGE2 in inhibiting acid secretion and stimulating mucus secretion respectively. When infused at a low dose, U-46619 inhibited acid secretion directly without causing a decrease in the ratio of mucosal blood flow to volume rate of secretion (R), this effect being similar to that observed for PGE2. However, unlike PGE2, U-46619 when administered in a higher dose caused a decline in R while decreasing acid secretion and mucosal blood flow, suggesting a primary restriction of blood flow. The antisecretory effects of arachidonic acid may be due in part to the endogenous formation of prostaglandin endoperoxides as opposed solely to prostaglandin formation. Considering the antisecretory and mucogenic actions of U-46619, nontoxic analogues of prostaglandin endoperoxides may be of value as antiulcer agents.
Similar content being viewed by others
References
Robert A, Nezamis JE, Phillips JP: Inhibition of gastric secretion by prostaglandins. Am J Dig Dis 12:1073–1076, 1967
Ramwell PW, Shaw JE: Prostaglandin inhibition of gastric secretion. J Physiol 195:34P-36P, 1968
Main IHM: Effects of prostaglandin E2 on the output of histamine and acid in rat gastric secretion induced by pentagastrin or histamine. Br J Pharmacol 36:214P-215P, 1969
Wilson DE, Levine RA: The effect of prostaglandin E1 on canine gastric acid secretion and gastric, mucosal blood flow. Am J Dig Dis 17:527–532, 1972
Classen M, Koch H, Deishle P, Weidenhiller S, Demling L: Wirkung von Prostaglandin E1 auf die basale Magensekretion des Menschen. Klin Wschr 48:876–878, 1970
Wilson DE, Phillips C, Levine RA: Inhibition of gastric secretion in man by prostaglandin A1. Gastroenterology 61:201–206, 1971
Robert A, magerlein BJ: 15-methyl PGE2 and 16,16-dimethyl PGE2: Potent inhibitors of gastric secretion. Adv Biosci 9:247–253, 1973
Karim SMM, Carter DC, Bhana D, Ganesan PA: Effect of orally administered prostaglandin E2 and its 15-methyl analogues on gastric secretion. Br Med J 1:143–146, 1973
Wilson DE, Winnan G, Quertermus J, Tao P: Effects of an orally administered prostaglandin analogue (16,16-dimethyl prostaglandin E2) on human gastric secretion. Gastroenterology 69:607–611, 1975
Ippoliti AF, Isenberg JI, Maxwell V, Walsh JH: The effect of 16,16-dimethyl prostaglandin E2 on meal-stimulated gastric acid secretion and serum gastrin in duodenal ulcer patients. Gastroenterology 70:488–491, 1976
Wilson DE, Quertermus J, Raiser M, Curran J, Robert A: Inhibition of stimulated gastric secretion by an orally administered prostaglandin capsule: A study in normal men. Ann Int Med 84:688–691, 1976
Fung WP, Lee SK, Karim SMM: Effect of prostaglandin 15(R)15 methyl-E2-methyl ester on the gastric mucosa, in patients with peptic ulceration—An endoscopic and histological study. Prostaglandins 5:465–472, 1974
Robert A: Antisecretory, antiulcer, cytoprotective and diarrheogenic properties, of prostaglandins. Adv Prostaglandin Thromboxane Res 2:507–520, 1976
Bolton JP, Palmer D, Cohen MM: Stimulation of mucus and nonparietal cell secretion by the E2 prostaglandins. Am J Dig Dis 23:359–364, 1978
Domschke W, Domschke S, Hornig D, Demling L: Prostaglandin-stimulated gastric mucus secretion in man. Acta Hepato-Gastroenterol 25:292–294, 1978
Bergstrom S: Prostaglandins: Members of a new hormonal system. Science 157:382–391, 1967
Coceani F, Pace-Asciak C, Volta F, Wolfe LS: Effect of nerve stimulation on prostaglandin formation and release from the rat stomach. Am J Physiol 213:1056–1064, 1967
Gorman R: Prostaglandin endoperoxides: Possible new regulators of cyclic nucleotide metabolism. J Cyclic Nucleotide Res 1:1–9, 1975
Hamberg M, Svensson J, Hedqvist P, Strandberg K, Samuelsson B: Involvement of endoperoxides and thromboxanes in anaphylactic reactions. Adv Prostaglandin Thromboxane Res 1:495–501, 1976
Samuelsson B, Hamberg M, Malmsten C, Svensson J: The role of prostaglandin endoperoxides and thromboxanes in platelet aggregation. Adv Prostaglandin Thromboxane Res 2:737–746, 1976
Conolly ME, Bieck PR, Payne NA, Adkins B, Oates JA: Effect of the prostaglandin precursor, arachidonic acid, on histamine stimulated gastric secretion in the conscious dog, and observations on the effect of inhibiting endogenous prostaglandin synthesis. Gut 18:429–437, 1977
Jacobson ED, Linford RH, Grossman MI: Gastric secretion in relation to mucosal blood flow studied by a clearance technic. J Clin Invest 45:1–13, 1966
Brodie BB, Axelrod J: The fate of aminopyrine (pyramidon) in man and methods for the estimation of aminopyrine and its metabolites in biological material. J Pharmacol Exp Ther 99:171–184, 1950
Jacobson ED: Comparison of prostaglandin E1 and norepinephrine on the gastric mucosal circulation. Proc Soc Exp Biol Med 133:516–519, 1970
Aminoff D: Methods for the quantitative estimation ofN-acetylneuraminic acid and their application to hydrolysates of sialomucoids. Biochem J 81:383–392, 1961
Glass GBJ: Mucosubstances of gastric secretion in man and their biological activity. Ann NY Acad Sci 106:775–793, 1963
Frame MH, Main IHM: A comparison of the effects of stable endoperoxide analogues with PGE2 and PGF2α on rat gastric ecretion, in vivo and in vitro. Br J Pharmacol 61:450P, 1977
Alter I, Kot PA, Ramwell PW, Rose JC, Shnider MR: Circulatory effects of prostaglandin endoperoxide analogues studied in the dog during left ventricular bypass. Br J Pharmacol 61:395–398, 1977
Thurston D, Tao P, Wilson DE: Cyclic nucleotides and the regulation of canine gastric acid secretion. Dig Dis Sci 24:257–264, 1979
Dozois RR, Dousa TP: Inhibition of guinea pig fundic gastric mucosa adenylate cyclase (AC) by prostaglandin precursors. Clin Res 25:607A, 1977
Chaudhury TK, Jacobson ED: Prostaglandin cytoprotection of gastric mucosa. Gastroenterology 74:59–63, 1978
Leader JP, Pereira JN: Stimulation of rat gastric mucus synthesis and secretion by prostaglandins. The Pharmacologist 26:209, 1978
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Tao, P., Scruggs, W. & Wilson, D.E. The effects of a prostaglandin endoperoxide analogue on canine gastric acid and mucus secretion. Digest Dis Sci 24, 449–454 (1979). https://doi.org/10.1007/BF01299826
Issue Date:
DOI: https://doi.org/10.1007/BF01299826