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.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]