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. 1986 May;88(1):19–23. doi: 10.1111/j.1476-5381.1986.tb09466.x

Mechanism of gastric antisecretory effect of SCH 28080.

W Beil, I Hackbarth, K F Sewing
PMCID: PMC1917128  PMID: 3011171

Abstract

The mechanism of the gastric antisecretory action of SCH 28080 has been studied utilizing two different in vitro test systems, isolated and enriched parietal cells from the guinea-pig and guinea-pig gastric membranes purified and enriched with K+/H+-ATPase. In guinea-pig isolated and enriched parietal cells SCH 28080 inhibited the acid response to histamine and high K+ concentrations with IC50 values not significantly different from each other. SCH 28080 inhibited the purified K+/H+-ATPase measured in the presence of 5 mM KCl with an IC50 value of 1.3 microM. Kinetic studies indicated a competitive inhibition of ATPase by SCH 28080 with respect to K+. Studies on Na+/K+-ATPase showed that this enzyme was only slightly depressed by SCH 28080. It is concluded that SCH 28080 acts with high selectivity on the parietal cell K%/H+-ATPase, establishing its antisecretory effect by a competitive interaction with the high affinity K+-site of the gastric ATPase.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Albinus M., Winne D. Subclasses of muscarinic receptors in isolated gastric mucosal cells: receptor characterization and parietal cell function. Eur J Pharmacol. 1983 Oct 28;94(3-4):281–295. doi: 10.1016/0014-2999(83)90417-x. [DOI] [PubMed] [Google Scholar]
  2. Beil W., Sewing K. F. Inhibition of partially purified K+/H+-ATPase from guinea-pig isolated and enriched parietal cells by substituted benzimidazoles. Br J Pharmacol. 1984 Jul;82(3):651–657. doi: 10.1111/j.1476-5381.1984.tb10803.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Black J. W., Duncan W. A., Durant C. J., Ganellin C. R., Parsons E. M. Definition and antagonism of histamine H 2 -receptors. Nature. 1972 Apr 21;236(5347):385–390. doi: 10.1038/236385a0. [DOI] [PubMed] [Google Scholar]
  4. Chiu P. J., Casciano C., Tetzloff G., Long J. F., Barnett A. Studies on the mechanisms of the antisecretory and cytoprotective actions of SCH 28080. J Pharmacol Exp Ther. 1983 Jul;226(1):121–125. [PubMed] [Google Scholar]
  5. Im W. B., Blakeman D. P., Mendlein J., Sachs G. Inhibition of (H+ + K+)-ATPase and H+ accumulation in hog gastric membranes by trifluoperazine, verapamil and 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate. Biochim Biophys Acta. 1984 Feb 29;770(1):65–72. doi: 10.1016/0005-2736(84)90074-9. [DOI] [PubMed] [Google Scholar]
  6. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  7. Long J. F., Chiu P. J., Derelanko M. J., Steinberg M. Gastric antisecretory and cytoprotective activities of SCH 28080. J Pharmacol Exp Ther. 1983 Jul;226(1):114–120. [PubMed] [Google Scholar]
  8. Nandi J., Ray T. K. Mechanism of action of gastric secretory inhibitors: effects of SCN- OCN-, NO-2, and NH+4 on (H+ + K+)-ATPase-mediated transport of H+ inside gastric microsomal vesicles. Arch Biochem Biophys. 1982 Jun;216(1):259–271. doi: 10.1016/0003-9861(82)90211-9. [DOI] [PubMed] [Google Scholar]
  9. Nandi J., Wright M. V., Ray T. K. Mechanism of gastric antisecretory effects of nolinium bromide. Gastroenterology. 1983 Oct;85(4):938–945. [PubMed] [Google Scholar]
  10. Saccomani G., Shah G., Spenney J. G., Sachs G. Characterization of gastric mucosal membranes. VIII. The localization of peptides by iodination and phosphorylation. J Biol Chem. 1975 Jun 25;250(12):4802–4809. [PubMed] [Google Scholar]
  11. Sachs G., Chang H. H., Rabon E., Schackman R., Lewin M., Saccomani G. A nonelectrogenic H+ pump in plasma membranes of hog stomach. J Biol Chem. 1976 Dec 10;251(23):7690–7698. [PubMed] [Google Scholar]
  12. Sanui H. Measurement of inorganic orthophosphate in biological materials: extraction properties of butyl acetate. Anal Biochem. 1974 Aug;60(2):489–504. doi: 10.1016/0003-2697(74)90259-0. [DOI] [PubMed] [Google Scholar]
  13. Sewing K. F., Harms P., Schulz G., Hannemann H. Effect of substituted benzimidazoles on acid secretion in isolated and enriched guinea pig parietal cells. Gut. 1983 Jun;24(6):557–560. doi: 10.1136/gut.24.6.557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Wallmark B., Sachs G., Mardh S., Fellenius E. Inhibition of gastric (H+ + K+)-ATPase by the substituted benzimidazole, picoprazole. Biochim Biophys Acta. 1983 Feb 9;728(1):31–38. doi: 10.1016/0005-2736(83)90433-9. [DOI] [PubMed] [Google Scholar]

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