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 ovary (CHO) cells. The deduced amino acid sequence was highly conserved as compared with those of the gastrin receptors in Mastomys enterochromaffin-like cells (90%) and canine parietal cells (89%). Human brain CCK-B receptors possessed slightly but significantly higher affinities for CCK-8 than for gastrin I, while both ligands bound equally to Mastomys enterochromaffin-like cell-derived gastrin receptors. Both CCK-8 and gastrin I markedly augmented phosphoinositide hydrolysis and cytosolic free calcium levels in the CHO transfectants, indicating that the cloned CCK-B receptor could functionally couple with intracellular signaling molecules. Moreover, CCK-8 and gastrin I dose-dependently increased [3H]thymidine incorporation of the CHO transfectants in serum-free medium and promoted cell growth. The CCK-B receptor mRNA was abundantly expressed in particular areas of the human brain and stomach, such 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 nervous system as well as digestive organs.
Ito
M
M
Third Division, Kobe University School of Medicine, Japan.
Matsui
T
T
Taniguchi
T
T
Tsukamoto
T
T
Murayama
T
T
Arima
N
N
Nakata
H
H
Chiba
T
T
Chihara
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D016466:CHO Cells; D002455:Cell Division / Q000187:drug effects; D002766:Cholecystokinin / Q000378:metabolism / Q000494:pharmacology*; D017124:Conserved Sequence; D006224:Cricetinae; D004247:DNA; D004261:DNA Replication / Q000187:drug effects; D004285:Dogs; D005755:Gastrins / Q000378:metabolism / Q000494:pharmacology*; D015723:Gene Library; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D009115:Muridae; D012333:RNA, Messenger / Q000378:metabolism*; D011949:Receptors, Cholecystokinin / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013936:Thymidine / Q000378:metabolism; D014162:Transfection
D005755:Gastrins; D012333:RNA, Messenger; D011949:Receptors, Cholecystokinin; D004247:DNA; D002766:Cholecystokinin; D013936:Thymidine