pH dependence of pepsinogen and acid secretion in isolated gastric glands

Rabbit isolated gastric glands were used to investigate the dependence of pepsinogen and acid secretions on extraglandular pH. Changing pH from 8.0 to 6.7 caused small increases in pepsinogen secretory responses to isoproterenol, carbachol, cholecystokinin octapeptide, Boots' secretin, and hyperosmolarity but caused large increases in responses to 8-bromoadenosine 3',5'-cyclic monophosphate (8BrcAMP), 8-bromoinosine 3',5'-cyclic monophosphate (8BrcIMP), and forskolin. The similar effect of pH on responses to 8BrcAMP, 8BrcIMP, and forskolin was suggested to reflect a commonality in their proposed mechanisms of action. It was concluded that reducing extraglandular pH indirectly caused an increase in activity of cAMP-dependent protein kinase or of a subsequent step in cAMP-dependent regulation of pepsinogen secretion. 8BrcAMP-stimulated acid secretion also increased as pH was changed from 8.0 to 6.7, and a similar explanation of the effect was suggested. However, histamine-stimulated acid secretion and adenyl cyclase activity decreased markedly as pH was lowered over this range. It was suggested that cAMP was rate limiting for stimulation by histamine and that the effect of pH on histamine-stimulated acid secretion could be attributed to an effect of pH on adenyl cyclase activity.