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Enhancing effect of staurosporine on NO production in rat peritoneal macrophages via a protein kinase C‐independent mechanism
Author(s) -
Sowa Grzegorz,
Przewłocki Ryszard
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb16649.x
Subject(s) - staurosporine , protein kinase c , mechanism (biology) , microbiology and biotechnology , protein kinase a , chemistry , kinase , biochemistry , biology , philosophy , epistemology
Staurosporine (3–100 nM), frequently used as a protein kinase C (PKC) inhibitor, increased accumulation of nitrite in the culture medium of rat peritoneal macrophages up to 6 times above the control level. Moreover, when used in combination with the stable analogue of cyclic AMP, dibutyryl‐cyclic AMP (db cyclic AMP; 0.1 mM), and/or a cytokine, tumour necrosis factor‐α (TNFα; 100 u ml −1 ), staurosporine synergistically potentiated, up to 30 times, nitrite accumulation. On the other hand, the other PKC inhibitors, calphostin C and H‐7 (10 nM‐10 μ m ) were not effective under the same conditions. The staurosporine‐induced nitrite accumulation, in both the presence and the absence of TNFα and/or db cyclic AMP was effectively inhibited by the protein synthesis inhibitor, cycloheximide, or by the nitric oxide (NO) synthesis inhibitor, N G ‐monomethyl‐L‐arginine (L‐NMMA). Thus our data suggest that staurosporine may enhance NO production in macrophages via intracellular mechanisms unrelated to the PKC inhibition.