Effects of Some Antisecretory Drugs on Acid Production, Intracellular Free Ca2+, and Cyclic AMP Production in Isolated Pig Parietal Cells

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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 ± 10−9 M for SCH 28080 and 1–3 ± 10−8 M for omeprazole. Ranitidine inhibited the histamine-stimulated but not the basal acid production. The IC50 value was 2 ± 10−5 M. Stimulation of acid production with carbachol was blocked by pirenzepine, with an IC50 of 6 ± 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.