CHARACTERIZATION OF CLONED HUMAN CHOLECYSTOKININ-B RECEPTOR AS A GASTRIN RECEPTOR

The cholecystokinin (CCK)-B receptor cloned from human brain was chara cterized as a gastrin receptor by using heterologous expression system s of COS-7 cells and Xenopus oocytes. I-125-gastrin binding to human C CK-B receptor expressed in COS-7 was time-dependent, saturable and als o specific, as well as (125)-I-CCK-8. The binding of I-125-gastrin was inhibited by CCK-8 about 10-fold more potently than by gastrin. The r ank order of potency of several antagonists to I-125-gastrin binding w as YM022 > CI-988 > L-365,260 > L-364,718. Addition of GTP gamma S, a nonhydrolysable analog of GTP, dose-dependently inhibited I-125-gastri n binding, and lowered the gastrin binding affinity, Gastrin (10(-9)-1 0(-7) M) also evoked a Ca2+-dependent Cl- current in Xenopus oocytes e xpressing CCK-B receptors. These results suggest that the pharmacologi cal profile of the cloned human CCK-B receptor using I-125-gastrin is closely parallel to that reported in gastric mucosa, and that the rece ptor transduces cellular signals of gastrin as well as those of CCK-8.