Cholecystokinin receptors on gallbladder muscle and pancreatic acinar cells: A comparative study

To compare receptors for cholecystokinin (CCK) in pancreas and gallbladder, we measured binding of ¹²⁵I-Bolton-Hunter-labeled CCK-8 (¹²⁵I-BH-CCK-8) to tissue sections from guinea pig gallbladder and pancreas under identical conditions. In both tissues, binding had similar time-, temperature-, and pH dependence, was reversible, saturable and inhibited only by CCK related peptides or CCK receptor antagonists. Autoradiography localized ¹²⁵I-BH-CCK-8 binding to the smooth muscle layer in the gallbladder. Binding of ¹²⁵I-BH-CCK-8 to gallbladder sections was inhibited by various agonists with the following potencies (IC₅₀): CCK-8 (0.4 nM) > des(SO₃)CCK-8 (0.07 μM) > gastrin-17-I (1.7 ± 0.3 μM) and by various receptor antagonists with the following potencies: L364,718 (1.5 nM) > CR 1409 (0.19 μM) > asperlicin = CBZ-CCK-(27-32)-NH₂ (1 μM) > Bt₂cGMP (120 μM). Similar potencies were found for the agonists and antagonists for pancreas sections. Inhibition of binding of ¹²⁵I-BH-CCK-8 by 11 different analogues of proglumide gave similar potencies for both pancreas and gallbladder. The potencies of agonists in stimulating and antagonists in inhibiting CCK-stimulated contraction or amylase release correlated closely with their abilities to inhibit ¹²⁵I-BH-CCK-8 binding to gallbladder or pancreas sections or acini, respectively. The present results demonstrate and characterize a method that can be used to compare the CCK receptors in guinea pig gallbladder and pancreas under identical conditions. Moreover, this study demonstrates that gallbladder and pancreatic CCK receptors have similar affinities for the various agonists and antagonists tested and, therefore, provides no evidence that they represent different subtypes of CCK receptors that can be distinguished pharmacologically.