The influence of adenine and guanine nucleotides on cholecystokinin (CCK) receptor binding was examined in streptolysin O-permeabilized rat pancreatic acini. Specific binding of tracer to intact acini was 12.1 +/- 0.4% per milligram protein, while permeabilized acini bound 34.6 +/- 2.9% (n = 7). The increase in binding was also seen when normalized to DNA. Binding to permeabilized acini was reduced by the presence of 1 mM ATP to 23.0 +/- 1.3%. Analysis of competitive inhibition of tracer binding by unlabeled CCK-8 was consistent with binding to two affinity states on intact acini, with the equilibrium dissociation constants for the high (KdH)- and low (KdL)-affinity states equal to 41 +/- 5 pM and 5.2 +/- 0.4 nM, respectively; permeabilized acini displayed a single binding site with Kd = 598 +/- 40 pM. In the presence of 1 mM ATP, two states were seen on permeabilized acini with KdH = 85 +/- 11 pM and KdL = 2.7 +/- 0.6 nM. ATP, ATP gamma S, GTP, and GTP gamma S all inhibited binding, with half-maximal inhibition occurring at greater than 1 mM, 21 microM, 5 microM, and 0.4 microM, respectively. GTP gamma S (1 microM) also induced two affinity states with KdH = 112 +/- 7 pM and KdL = 1.5 +/- 0.2 nM (n = 3). Binding of CCK to pancreatic membranes was also decreased by ATP, and a similar regeneration of two binding affinity states was observed. ATP also decreased binding of [125I-Tyr4]bombesin to permeabilized acini, but in contrast did not generate two measurable binding affinity states.(ABSTRACT TRUNCATED AT 250 WORDS)