Dependence on extracellular Ca2+ for the effects of cholecystokinin-8 in rat pancreatic islets.
The dependence on extracellular Ca2+ for the insulinotropic effect of cholecystokinin-8 (CCK-8) and CCK-8-induced cellular events in isolated rat islets was investigated. CCK-8 stimulated insulin secretion at 8.3 mM glucose in the presence but not in the absence of extracellular Ca2+. In contrast, efflux of 45Ca2+ from 45Ca(2+)-prelabelled islets was stimulated by CCK-8 to the same extent in the presence as in the absence of extracellular Ca2+. This shows that CCK-8 mobilizes intracellularly stored Ca2+. CCK-8 also stimulated 3H-efflux from myo-[2-3H]inositol-prelabelled islets showing that the peptide activates phosphoinositide (PI) hydrolysis. The PI-hydrolysis persisted, but was reduced, in the absence of extracellular Ca2+. This suggests that PI-hydrolysis might underly the liberation of intracellularly stored Ca2+ induced by CCK-8. CCK-8 also stimulated 86Rb(+)-efflux (reflecting K(+)-movements) from 86Rb(+)-prelabelled islets. This effect was clearly reduced, but not absent, in a Ca(2+)-deficient medium, suggesting opening of Ca(2+)-dependent K(+)-channels. Our results show that although CCK-8 mobilizes intracellularly stored Ca2+ and stimulates PI-hydrolysis also in the absence of extracellular Ca2+, the insulinotropic effect of CCK-8 requires the presence of extracellular Ca2+.
Karlsson
S
S
Department of Pharmacology, Lund University, Sweden.
Ahrén
B
B
D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D007700:Kinetics; D008297:Male; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012413:Rubidium / Q000378:metabolism; D012844:Sincalide / Q000494:pharmacology*
D007328:Insulin; D010716:Phosphatidylinositols; D005947:Glucose; D012844:Sincalide; D012413:Rubidium; D002118:Calcium