EFFECTS OF PHORBOL ESTER ON CHOLECYSTOKININ OCTAPEPTIDE-EVOKED EXOCRINE PANCREATIC-SECRETION IN THE RAT

1. A comparative study was made of the effect of the phorbol ester, 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) on cholecystokinin octapeptide‐evoked exocrine pancreatic secretion in the anaesthetized rat and isolated permeabilized pancreatic acinar cells. 2. Cholecystokinin octapeptide (CCK8; 0.10‐6.40 nmol (kg body weight)‐1) induced dose‐dependent increases in pancreatic juice flow, total protein output and amylase release in the anaesthetized rat. 3. Administration of TPA (10(‐8) mol (kg body weight)‐1) in combination with CCK8 resulted in marked attenuation of the CCK8‐evoked secretory response. 4. Simultaneous injection of polymyxin B (10(‐8) mol (kg body weight)‐1), an inhibitor of protein kinase C, with TPA and CCK8 reversed the inhibitory effect of the phorbol ester on CCK8‐induced pancreatic juice flow, total protein output and amylase release. 5. In permeabilized rat pancreatic acini CCK8 (10(‐13)‐10(‐9) M) elicited dose‐dependent increases in [3H]leucine‐labelled protein secretion (3H‐labelled protein release). Combining TPA (10(‐8) M) with CCK8 resulted in an inhibition of the CCK8‐induced 3H‐labelled protein release especially at lower concentrations of CCK8. At higher concentrations of CCK8, TPA was unable to inhibit the CCK8‐evoked 3H‐labelled protein release. Again, polymyxin B reversed the TPA‐induced inhibition of CCK8‐evoked 3H‐labelled protein output. 6. The results indicate that protein kinase C activation may play an important physiological role in modulating the CCK8‐evoked secretory response in rat pancreas in vivo and in vitro. © 1990 The Physiological Society