Cholecystokinin receptors.
Wank, Stephen A.
Digestive Diseases Branch, National Institute of Diabetes and
Digestive and Kidney Diseases, National Institutes of Health,
Bethesda, Maryland 20892-1804
APStracts 2:0168G, 1995.
The cholecystokinin and gastrin families of peptides act as hormones
and neuropeptides on central and peripheral CCK receptors to mediate
secretion and motility in the gastrointestinal (GI) tract in the
physiologic response to a normal meal. CCK and it's receptors are
also widely distributed in the central nervous system and contribute
to the regulation of satiey, anxiety, analgesia and dopamine-mediated
behavior. Although the wide distribution, myriad number of functions
and reported pharmacological heterogeneity of CCK receptors would
suggest a large number of receptor subyptes, the application of
modern molecular biological techniques has identified two
cholecystokinin receptors, CCKAR and CCKBR, that mediate the actions
of CCK and gastrin, having found that gastrin receptors are identical
to CCKBRs. CCKARs, found predominantly in the GI system and select
areas of the CNS, have high affinity for CCK and the nonpeptide
antagonist, L-364,718 while CCKBRs, found predominantly in the CNS
and select areas of the GI system have high affinity for CCK and
gastrin and the nonpeptide antagonist, L365,260. Both CCKAR and CCKBR
are highly conserved between species although there is some tissue
specific variation in expression. Recombinant receptor expression
faithfully reproduces the native receptor pharmacology and signal
transduction pathways allowing direct comparisons of receptor
function between species as well as a convenient source of receptor.
Our present knowledge of the chromosomal localization, receptor gene
structure and primary sequence will allow further studies in disease
association, receptor regulation and structure-function analysis.
Received 7 August 1995; accepted in final form 8 August 1995.
APS Manuscript Number G331-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 August 1995.