Effects of some antisecretory drugs on acid production, intracellular free Ca2+, and cyclic AMP production in isolated pig parietal cells

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.