Chelerythrine inhibits the secretory response of human blood platelets without specifically inhibiting protein kinase C.
Chelerythrine (chloride) has previously been documented to be a potent and selective inhibitor of the serine/threonine-specific protein kinase C (PKC). In this study, it was shown that 10 microM chelerythrine completely inhibited serotonin secretion and partially inhibited phosphatidic acid formation in human blood platelets activated by thrombin (1U/ml). However, there was no effect on PKC activity as assessed by the level of phosphorylation of the 47K protein. Therefore, chelerythrine has been shown not to be a specific inhibitor of PKC. Without specifically affecting PKC activity, it is nevertheless capable of completely inhibiting platelet secretion, indicating that it may affect the signal transduction pathway responsible for platelet secretion at a point downstream or independent of PKC.
Lane
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Sir William Dunn School of Pathology, University of Oxford, United Kingdom.
Novales-Li
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D000470:Alkaloids; D053119:Benzophenanthridines; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D010617:Phenanthridines / Q000494:pharmacology*; D010712:Phosphatidic Acids / Q000097:blood; D010766:Phosphorylation; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000097:blood; D012701:Serotonin / Q000097:blood / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013917:Thrombin / Q000494:pharmacology
D000470:Alkaloids; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D010617:Phenanthridines; D010712:Phosphatidic Acids; D012701:Serotonin; C016299:chelerythrine; D011493:Protein Kinase C; D013917:Thrombin