INVOLVEMENT OF G-PROTEINS IN THE EFFECT OF CARBACHOL AND CHOLECYSTOKININ IN RAT PANCREATIC-ISLETS

Phospholipase C is involved in the insulinotropic effect of carbachol (CCh) and cholecystokinin octapeptide (CCK-8). The involvement of the type of G protein was investigated in rat pancreatic islets. Guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S; a nonhydrolyzable GTP analogu e) increased insulin release in electrically permeabilized islets. Bot h CCh and CCK-8 increased the GTP gamma S effect indicative of an invo lvement 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 C Ch, the CCK-8 effect on both insulin release and IP3 levels of islets was not modified by a PT pretreatment at various glucose concentration s. Two types of experiments indicate the type of G; protein involved: first, long-term agonistic stimulation by either CCh or CCK-8 led to a downregulation of alpha(0) and alpha(q/11), respectively; second, int roduction of specific anti-alpha(0) or -alpha(q/11) antibodies into el ectrically permeabilized islets nearly completely abolished the effect s of CCh and CCK-8, respectively. The data indicate that both CCh and CCK-8 act as insulinotropic agents via the phospholipase C system; in the effect of CCh the PT-sensitive a, and in the effect of CCK-8 the P T-insensitive alpha(q/11) is involved.