Role of protein kinase C in histamine release from human basophils.
In this study, we investigated the role of calcium and phospholipid-dependent protein kinase (protein kinase C, PKC) in the modulation of histamine release from human basophils. A novel and potent inhibitor of PKC, K-252a, inhibited the release of histamine induced by anti-IgE in a dose-dependent manner with ID50 (the dose required for 50% inhibition of histamine release) of 2.2 x 10(-8) M. Histamine release stimulated with 12-0-tetradecanoyl-phorbol-13-acetate(TPA) was also suppressed by K-252a with maximal inhibition of 48.0 +/- 9.3% at 10(-7) M. In contrast, K-252a did not inhibit the release of histamine in response to FMLP and ionophore A23187. Another inhibitor of PKC, H-7, exhibited a dose-dependent inhibition of anti-IgE-induced histamine release with ID50 of 8.6 x 10(-4) M. H-8 and HA1004, which closely resemble H-7 in chemical structure but are less potent in inhibiting PKC, did not inhibit histamine release stimulated with anti-IgE, but rather enhanced the release at higher concentrations. These results strongly suggest that PKC activation plays a crucial role in the mediation of IgE-mediated histamine release from human basophils.
D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D001491:Basophils / Q000378:metabolism* / Q000502:physiology; D002227:Carbazoles / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology / Q000494:pharmacology; D026121:Indole Alkaloids; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D000888:Antibodies, Anti-Idiotypic; D002227:Carbazoles; D026121:Indole Alkaloids; C026408:anti-IgE antibodies; D007073:Immunoglobulin E; C049985:staurosporine aglycone; D011493:Protein Kinase C