EFFECTS OF PHORBOL ESTERS AND SECRETIN ON PANCREATIC-JUICE SECRETION IN THE ANESTHETIZED RAT

1. An investigation was made of the effects of phorbol esters, 12-O-tetradeconylphorbol acetate (TPA) and secretin on pancreatic juice secretion in the anaesthetized rat. TPA (10-12-10-8 mol/kg body wt) evoked marked dose-dependent increases in secretory rate and total protein output. 2. An inactive phorbol ester (4α-phorbol-12-13-didecanoate; 4αPDD) had no effect on the secretory rate but increased total protein output compared to saline control animals. 3. When TPA was administered in combination with the protein kinase C inhibitor, Polymyxin B (10-8 mol/kg body wt) both secretory rate and protein output were significantly reduced (P < 0.001) compared to TPA alone. 4. Secretin (50-1600 pmol/kg body wt) increased both pancreatic juice flow and total protein output in a dose-dependent manner. 5. Simultaneous administration of secretin (50-1600 pmol/kg body wt) and TPA (10-10 mol/kg body wt) resulted in a marked attenuation in the secretin-induced secretory rate while secretin-evoked protein output was unaffected. 6. The results indicate that protein kinase C activation is associated with pancreatic juice secretion and it may also modulate secretin-induced pancreatic juice flow in the anaesthetized rat. © 1990.