EFFECTS OF CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE-IV INHIBITOR, RO-20,1724, ON PANCREATIC EXOCRINE SECRETION IN DOG

1. The effects of the cyclic nucleotide phosphodiesterase (PDE) inhibi tors, Ro20,1724, 3-isobutyl-1-methylxanthine (IBMX), trifluoperazine ( TFP) and amrinone on pancreatic exocrine secretion were investigated i n anaesthetized dogs in comparison with those of secretin and cholecys tokinin octapeptide (CCK-8). 2. Ro20,1724(1-30 nmol/kg), IBMX (3-30 nm ol/kg), secretin (0.01-0.1 pmol/kg) or CCK-8 (0.1-1 pmol/kg) injected i.a. elicited a dose-dependent increase in the secretion of pancreatic juice, but TFP and amrinone (up to 1 mu mol/kg) did not. 3. The bicar bonate concentration in pancreatic juice was increased and the protein concentration was decreased by Ro20,1724, IBMX and secretin. Cholecys tokinin octapeptide increased the protein concentration but did not al ter the bicarbonate concentration. 4. Ro20,1724 and IBMX elicited more than the respective additive secretory response when added together w ith secretin, although the stimulatory effects of CCK-8 with Ro20,1724 and IBMX were additive. 5. Ro20,1724 and IBMX increased cyclic AMP co ncentration but did not affect cyclic GMP concentration. 6. These resu lts suggest that Ro20,1724 and IBMX have secretory properties on pancr eatic exocrine glands of the dog, which may be mediated through an inc rease in cyclic AMP subsequent to inhibition of PDE activity. Furtherm ore, pancreatic PDE enzymes in the dog may be mainly type IV.