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Interaction of chelerythrine with inositol phosphate metabolism
Author(s) -
Le Corvoisier Philippe,
Lacotte Jérôme,
Laplace Monique,
Crozatier Bertrand
Publication year - 2002
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1046/j.1472-8206.2002.00069.x
Subject(s) - chelerythrine , inositol phosphate , inositol , chemistry , protein kinase c , pharmacology , phosphatase , metabolism , kinase , biochemistry , phosphorylation , biology , receptor
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 IP 3 into IP 2 ) was completely blocked and we observed a large increase in IP accumulation limited to IP 2 without any increase in IP 3 , 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.