[Ca2+]i‐ and insulin‐stimulating effect of the non‐membranepermeable phosphatase‐inhibitor microcystin‐LR in intact insulin‐secreting cells (RINm5F)

Autor: Leiers, T, Bihlmayer, A, Ammon, H P T, Wahl, M A
Zdroj: British Journal of Pharmacology; July 2000, Vol. 130 Issue: 6 p1406-1410, 5p
Abstrakt: Microcystin‐LR, a specific and effective inhibitor of serine/threonine phosphatases type 1/2A which does not permeate cells, was used to distinguish intracellular and extracellular effects of phosphatase inhibitors on insulin secretion by RINm5F cells.Incubation of intact RINm5F cells with microcystin‐LR (0.1–2 μM) almost doubled basal insulin release at 3 mMglucose but left maximal insulin release induced by KCl (30 mM) unaffected.In parallel, there was an increase in cytosolic Ca2+by up to half maximum, which could be suppressed by the Ca2+‐channel blocker D600.In contrast, microcystin‐LR incubation of intact cells did not affect phosphatase activity but significantly reduced phosphatase activity when used in cellular fractions.From these data we conclude that microcystin‐LR could affect Ca2+‐channels and insulin release by inhibiting an extracellular phosphatase‐like activity.
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