Involvement of g-proteins in the effect of carbachol and
cholecystokinin in rat pancreatic islets.
Verspohl, E. J., and K. Herrmann.
Department of Pharmacology, Institute of Pharmaceut. Sci.,
University of Muenster, Germany
APStracts 3:0042E, 1996.
Phospholipase C is involved in the insulinotropic effect of carbachol
(CCh)- and cholecystokinin-8 (CCK8). The involvement of the type of
G-protein was investigated in rat pancreatic islets. GTPsS (a non
-hydrolyzable GTP analog) increased insulin release in electrically
permeabilized islets. Both CCh and CCK8 increased the GTPsS effect
indicative of an involvement of G-proteins. Pretreatment of the
islets with pertussis toxin (PT) impaired the CCh-induced insulin
secretion in the presence of 3.0 mM glucose and inhibited the
stimulatory CCh effect on inositol-(1,4,5)-trisphosphate (IP3) levels
at low and high glucose. In contrast to CCh, the CCK8 effect on both
insulin release and IP3 levels of islets was not modified by a PT
-pretreatment at various glucose concentrations. Two types of
experiments indicate the type of G-protein involved: first, long-term
agonistic stimulation by either CCh or CCK8 led to a downregulation
of [alpha]o and [alpha]q/11, respectively; second, introducing
specific anti-[alpha]o or [alpha]q/11 antibodies into electrically
permeabilized islets nearly completely abolished the effects of CCh
and CCK8, respectively. The data indicate that both CCh and CCK8 act
as insulinotropic agents via the PLC-system; in the effect of CCh the
PT-sensitive [alpha]o and in the effect of CCK8 the PT-insensitive
[alpha]q/11 is involved.
Received 18 July 1995; accepted in final form 19 February 1996.
APS Manuscript Number E336-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 March 96