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 analogue) increased insulin release in electrically permeabilized islets. Both CCh and CCK-8 increased the GTP gamma S 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 CCK-8 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 CCK-8 led to a downregulation of alpha o and alpha q/11, respectively; second, introduction of specific anti-alpha o or -alpha q/11 antibodies into electrically permeabilized islets nearly completely abolished the effects 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 alpha o and in the effect of CCK-8 the PT-insensitive alpha q/11 is involved.
Verspohl
E J
EJ
Department of Pharmacology, University of Muenster, Germany.
Herrmann
K
K
D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology*; D005947:Glucose / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D037342:Pertussis Toxin; D051381:Rats; D017208:Rats, Wistar; D012844:Sincalide / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D007328:Insulin; D010566:Virulence Factors, Bordetella; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D005947:Glucose; D012844:Sincalide