Journal
BRITISH JOURNAL OF PHARMACOLOGY
Volume 130, Issue 6, Pages 1406-1410Publisher
WILEY-BLACKWELL
DOI: 10.1038/sj.bjp.0703441
Keywords
serine/threonine phosphatase; phosphatase inhibition; microcystin-LR; insulin release; insulin-secreting cells; cytosolic calcium
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1 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. 2 Incubation of intact RINm5F cells with microcystin-LR (0.1-2 mu M) almost doubled basal insulin release at 3 mM glucose but left maximal insulin release induced by KCl (30 mM) unaffected. 3 In parallel, there was an increase in cytosolic Ca2+ by up to half maximum, which could be suppressed by the Ca2+-channel blocker D600. 4 In contrast, mitrocystin-LR incubation of intact cells did not affect phosphatase activity but significantly reduced phosphatase activity when used in cellular fractions. 5 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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