FUNCTIONAL-CHARACTERIZATION OF A HUMAN BRAIN CHOLECYSTOKININ-B RECEPTOR - A TROPHIC EFFECT OF CHOLECYSTOKININ AND GASTRIN

We have cloned a human brain cholecystokinin (CCK)-B receptor cDNA and characterized its function by introducing it into Chinese hamster ova ry (CHO) cells. The deduced amino acid sequence was highly conserved a s compared with those of the gastrin receptors in Mastomys enterochrom affin-like cells (90%) and canine parietal cells (89%). Human brain CC K-B receptors possessed slightly but significantly higher affinities f or CCK-8 than for gastrin I, while both ligands bound equally to Masto mys enterochromaffin-like cell-derived gastrin receptors. Both CCK-8 a nd gastrin I markedly augmented phosphoinositide hydrolysis and cytoso lic free calcium levels in the CHO transfectants, indicating that the cloned CCK-B receptor could functionally couple with intracellular sig naling molecules. Moreover, CCK-8 and gastrin I dose-dependently incre ased [H-3]thymidine incorporation of the CHO transfectants in serum-fr ee medium and promoted cell growth. The CCK-B receptor mRNA was abunda ntly expressed in particular areas of the human brain and stomach, suc h as the cerebral cortex and mucosa of the gastric fundus. This is the first demonstration of trophic effects of CCK and gastrin through the normal human brain CCK-B receptor. The availability of this receptor cDNA will help to clarify the precise role of CCK in the central nervo us system as well as digestive organs.