We investigated the regulatory effect of cholecystokinin (CCK) on subsequent insulin binding to pancreatic acinar cells. Rat isolated acini were preincubated with various concentrations of CCK octapeptide (CCK-8) at 37 degrees C. Acini were then washed, resuspended in the binding buffer, and incubated with 8.3 pM 125I-labeled insulin for 60 min at 37 degrees C. Pretreatment with CCK-8 caused inhibition of subsequent 125I-insulin binding that was time and concentration dependent. Significant inhibition was observed with 3 pM CCK-8. Computer analysis of the competition-inhibition study with a nonlinear least-squares curve-fitting program revealed that CCK-8 pretreatment of acini reduced the receptor affinity of the high-affinity binding site. This inhibitory action of CCK-8 was not due to the alteration in degradation or internalization of the tracer. When acini were pretreated with 100 pM CCK-8 for 120 min at 4 degrees C, a reduction in the receptor affinity of the high-affinity binding site was also observed. In pancreatic membrane prepared from acini preincubated with 100 pM CCK-8 for 120 min at 37 degrees C, displacement of 125I-insulin (83 pM) by unlabeled insulin (24 degrees C, 1 h) revealed that CCK-8 inhibited 125I-insulin binding by altering the receptor affinity of the high-affinity binding site. In acinar preparations the inhibitory effect of CCK-8 on 125I-insulin binding was abolished when acini were preincubated with CCK-8 and CCK receptor antagonist L 374718 at 37 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)