Effect of secretin and caerulein in canine pancreas: relation to prostaglandins.

We investigated the effect of secretin and caerulein on pancreatic circulation and exocrine secretion and its relation to prostaglandin (PG) synthesis by studying the effect of these peptides on the pancreatic blood flow and the flow rate of pancreatic exocrine secretion in the isolated blood-perfused pancreas of pentobarbital-anesthetized dogs without or with pretreatment with the cyclooxygenase inhibitors, indomethacin and meclofenamate. Intra-arterial administration of secretin (0.1-0.3 U/kg) produced an initial vasoconstriction followed by vasodilation. On the other hand, caerulein (50-200 ng/kg) produced vasodilation and increased pancreatic blood flow in a dose-related manner. Both secretin and caerulein increased the flow rate of pancreatic exocrine secretion. In animals pretreated with either indomethacin or meclofenamate, the ability of secretin to produce an initial vasoconstriction was abolished and the subsequent vasodilator component of the response as well as caerulein-induced vasodilation were reduced in duration. The effect of caerulein but not of secretin to stimulate the flow rate of pancreatic exocrine secretion was reduced by indomethacin and meclofenamate. Administration of PGI2 and PGE2 into the pancreas caused vasodilation, whereas PGF2 alpha and PGD2 produced a biphasic effect, i.e., an initial vasoconstriction followed by vasodilation. Infusion of either PGI2 or PGE2 but not that of PGF2 alpha or PGD2 minimized the effect of cyclooxygenase inhibitors to reduce the duration of vasodilator response elicited by secretin and caerulein. Prostaglandins neither altered the basal nor the rise in flow rate of pancreatic exocrine secretion produced by secretin and caerulein. These data indicate that in the canine pancreas prostaglandins contribute to the effects of secretin and caerulein to increase pancreatic blood flow but not to their effect on pancreatic exocrine secretion.