PD-135158, A CCK(B) GASTRIN RECEPTOR ANTAGONIST, STIMULATES RAT PANCREATIC-ENZYME SECRETION AS A CCK(A) RECEPTOR AGONIST

The CCK(B)/gastrin receptor antagonist, PD 135158 (CAM 1208), surprisi ngly stimulates lipase release from isolated rat pancreatic acini dose dependently in a biphasic manner, with identical efficacy but lower p otency compared to cholecystokinin octapeptide (CCK-8). Half-maximal s timulation occurred at 0.6 muM and maximal secretion was induced at 50 muM. Supramaximal concentrations decreased lipase release. Acinar lip ase secretion in response to 25 pM CCK-8 or 1 muM CAM-1028 was abolish ed by 5 muM of the specific CCK, receptor antagonist loxiglumide (CR 1 505), half-maximal inhibition was observed at 0.6 muM for CCK-8 and 0. 4 muM for PD 135158. These data demonstrate that the CCK(B)/gastrin re ceptor antagonist, PD 135158, acts as a full agonist at the rat pancre atic CCK(A) receptor.