Differences in Partial Agonist Action at Cholecystokinin Receptors of Mouse and Rat Are Dependent on Parameters Extrinsic to Receptor Structure: Molecular Cloning, Expression and Functional Characterization of the Mouse Type A

The mouse cholecystokinin (CCK) receptor is functionally dis-tinct from the extensively studied rat receptor on the basis of differences in binding and biological activity of phenethyl ester analogs of CCK. These are partial agonists at the rat receptor and full agonists at the mouse pancreatic receptor. To explore this, we cloned the cDNA for the mouse type A CCK receptor, established a receptor-bearing Chinese hamster ovary (CHO) cell line and characterized its binding and biological character-istics. Despite 25 differences in amino acid sequence from the rat receptor, including a seven-amino acid insertion in the third intracellular loop, mouse and rat receptors were functionally indistinguishable when expressed in CHO cells. Of note, in the mouse pancreatic cell environment, a stable analog of guanosine triphosphate significantly inhibited binding of CCK