Investigations with the selective PKC inhibitor chelerythrine on human basophils.
Modulation of protein kinase C (PKC) activity in basophils (B) can influence IgE-mediated histamine release (HR). The present study investigated the effects of chelerythrine, which inhibits isolated PKC (IC50 0.7 microM), on different activation pathways in B. Fc epsilon RI-mediated HR was strongly inhibited by chelerythrine (86.5 +/- 5.4%, 5 microM, n = 11). TPA-induced mediator release was also suppressed: 77.1 +/- 8.5% inhibition (7.5 microM). HR due to non-immunological stimuli (A23187, FMLP) was strongly inhibited by chelerythrine. Previously, other selective PKC-inhibitors have been shown to potentiate IgE-mediated HR from B suggesting a negative modulatory role of PKC, whereas non-specific inhibitors such as staurosporine inhibited HR. Chelerythrine might therefore be less selective for PKC. This may be indicated by the fact that chelerythrine inhibits PKC at its catalytic domain, which is homologous with other protein kinases.
von Stebut
E
E
Dept. of Dermatology, University of Lübeck, Germany.
Amon
U
U
Herbert
J M
JM
Wolff
H H
HH
D000470:Alkaloids / Q000494:pharmacology; D001491:Basophils / Q000187:drug effects / Q000201:enzymology*; D053119:Benzophenanthridines; D000001:Calcimycin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D066298:In Vitro Techniques; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010617:Phenanthridines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors / Q000494:pharmacology
D000470:Alkaloids; D053119:Benzophenanthridines; D010617:Phenanthridines; D007073:Immunoglobulin E; D000001:Calcimycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; C016299:chelerythrine; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate