Effects of some antisecretory drugs on acid production, intracellular free Ca2+, and cyclic AMP production in isolated pig parietal cells |
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Authors: | S M?rdh Y H Song B Wallmark |
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Affiliation: | Dept. of Medical and Physiological Chemistry, Uppsala University, Sweden. |
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Abstract: | The effects of some inhibitors of acid secretion were tested on isolated, purified pig parietal cells. The cells were stimulated with 10(-4) M histamine, 10(-5) M carbachol, or 10(-7) M pentagastrin. The H,K-ATPase inhibitors SCH 28080 and omeprazole inhibited both the basal and secretagogue-stimulated acid production, as measured by aminopyrine accumulation, irrespective of the type of stimulator used. The IC50 value was 3-5 x 10(-9) M for SCH 28080 and 1-3 x 10(-8) M for omeprazole. Ranitidine inhibited the histamine-stimulated but not the basal acid production. The IC50 value was 2 x 10(-5) M. Stimulation of acid production with carbachol was blocked by pirenzepine, with an IC50 of 6 x 10(-7) M. Pirenzepine (10(-5) M) specifically blocked the carbachol-stimulated increase in cytosolic free Ca2+ in fura-2-loaded cells but not the increase in cytosolic free Ca2+ induced by histamine or pentagastrin. Ranitidine (10(-4) M) prevented the histamine-induced increase in Ca2+ and was also the only one of the four inhibitors which prevented the histamine-stimulated cAMP formation. SCH 28080 (10(-5) M) significantly potentiated the histamine-stimulated increase in cytosolic free Ca2+ and the formation of cAMP, whereas omeprazole (10(-5) M) was without effect. |
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