Characterization of cloned human cholecystokinin-B receptor as a gastrin receptor.

The cholecystokinin (CCK)-B receptor cloned from human brain was characterized as a gastrin receptor by using heterologous expression systems of COS-7 cells and Xenopus oocytes. 125I-gastrin binding to human CCK-B receptor expressed in COS-7 was time-dependent, saturable and also specific, as well as 125-I-CCK-8. The binding of 125I-gastrin was inhibited by CCK-8 about 10-fold more potently than by gastrin. The rank order of potency of several antagonists to 125I-gastrin binding was YM022 > CI-988 > L-365,260 > L-364,718. Addition of GTP gamma S, a nonhydrolysable analog of GTP, dose-dependently inhibited 125I-gastrin binding, and lowered the gastrin binding affinity, Gastrin (10(-9)-10(-7) M) also evoked a Ca(2+)-dependent Cl- current in Xenopus oocytes expressing CCK-B receptors. These results suggest that the pharmacological profile of the cloned human CCK-B receptor using 125I-gastrin is closely parallel to that reported in gastric mucosa, and that the receptor transduces cellular signals of gastrin as well as those of CCK-8.