Separate activation sites for cholecystokinin and bombesin on pancreatic acini: an electrophysiological study employing a competitive antagonist for the action of CCK.

The effects of dibutyryl cyclic guanosine 3':5' monophosphate (dbcGMP) on the electrical responses of in vitro mouse pancreatic acinar cells to caerulein, bombesin and acetylcholine, applied by microionophoresis, were investigated using intracellular microelectrode recordings. Exposure to dbcGMP (10(-3) mol . 1-1) quickly abolished the depolarization response to caerulein ionophoresis, while the bombesin-nonapeptide and acetylcholine-induced depolarizations were retained. Exposing acinar cells to 2 x 10(-4) mol . 1-1 dbcGMP reduced their sensitivity such that a 10-fold increase in the applied caerulein ionophoresis current was required to restore the responses to the same magnitude as those obtained in a dbcGMP-free environment. The response to topical applications of pentagastrin and CCK-33 were also abolished by dbcGMP. The results provide direct evidence that functional ACh, bombesin and CCK receptors are all present within the same acinar cell unit. The dbcGMP-induced inhibition of responses evoked by CCK-like peptides is immediate, specific and easily reversible. DbcGMP acts as a competitive antagonist of the CCK receptor on pancreatic acinar cells.