Effect of Bt2cGMP on action of cholecystokinin in isolated perfused rat pancreas.

We have examined the effects of Bt2cGMP on cholecystokinin stimulation of pancreatic exocrine secretion in the isolated perfused rat pancreas. Bt2cGMP produced a concentration-dependent inhibition of the stimulatory effects of cholecystokinin octapeptide (CCK-8, 100 pM) on both pancreatic juice flow and enzyme secretion. Adding 1 mM Bt2cGMP rapidly and completely abolished CCK-8-stimulated pancreatic juice and enzyme secretion. Adding 500 microM Bt2cGMP for 10 min at the termination of 1 nM of CCK-8 infusion caused an immediate and persistent inhibition of the residual response. In contrast, treatment with C-terminal CCK antiserum I had no influence on the residual response. To account for the ability of Bt2cGMP to function as a competitive antagonist of the action of CCK and the ability of the nucleotide to inhibit the residual stimulation caused by CCK, we feel that Bt2cGMP hindered the binding of CCK not only by reducing the association rate constant for hormone binding but also accelerating the dissociation rate.