Role of prostaglandin E2 in stimulus-secretion coupling in rat exocrine pancreas

Secretin (5 x 10(-9)-5 x 10(-7) M) increased enzyme secretion as well as cellular adenosine 3',5'-cyclic monophosphate (cyclic AMP) in a concentration-dependent manner in dispersed rat pancreatic acini. On the other hand, prostaglandin E2 (10 micrograms/ml) induced an accumulation of the cellular cyclic AMP as observed by secretin (5 x 10(-7) M) but did not stimulate enzyme secretion. Furthermore, 10 micrograms/ml prostaglandin E2 had a small inhibitory effect on the amylase release induced by maximal stimulation of secretin (5 x 10(-7) M), although the combination of prostaglandin E2 and secretin caused a bigger increase in the cellular cyclic AMP than that induced by each alone (additive effect). An inhibitory effect of prostaglandin E2 was also observed on the amylase release induced by maximal stimulation of caerulein (10(-10) M). Prostaglandin E2 had no effect on either the resting or the caerulein-stimulated free cytosolic calcium concentration of the acinar cells measured using fura-2. These results suggest that the inhibitory effect is accounted for by the functionally compartmentalized cyclic AMP produced by prostaglandin E2 or by another noncalcium mobilizing mechanism.