PMID: 11903510Mar 21, 2002Paper

Interaction of chelerythrine with inositol phosphate metabolism

Fundamental & Clinical Pharmacology
Philippe Le CorvoisierBertrand Crozatier

Abstract

Chelerythrine, a potent inhibitor of protein kinase C (PKC), was evaluated for its effect on inositol phosphate (IP) metabolism in newborn rat cardiomyocytes in culture. In a first step, we evaluated the effect of chelerythrine on IP accumulation in basal conditions. For a 10(-4) M dose, 5-phosphatase activity (which dephosphorylates IP3 into IP2) was completely blocked and we observed a large increase in IP accumulation limited to IP2 without any increase in IP3, strongly suggesting that chelerythrine at this dose modifies IP metabolism. At a lower dose (10(-5) M) of chelerythrine, which did not modify IP accumulation and 5-phosphatase activity in basal conditions, the response to angiotensin II stimulation was completely abolished by the addition of chelerythrine. We conclude thus that chelerythrine, even at 10(-5) M, interacts markedly with IP metabolism, and caution should be exerted when interpreting the results obtained with this drug, which is still currently used at this dose.

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Citations

Mar 14, 2003·Free Radical Biology & Medicine·Florian GuthmannBernd Rüstow
May 27, 2004·Natural Product Reports·Kenneth W Bentley
Sep 27, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Karin PrzyklenkPeter Whittaker

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