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  • Title: Dependence on extracellular Ca2+ for the effects of cholecystokinin-8 in rat pancreatic islets.
    Author: Karlsson S, Ahrén B.
    Journal: Diabetes Res; 1991 Mar; 16(3):139-43. PubMed ID: 1666346.
    Abstract:
    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+.
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