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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 × 10‐8M. 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 lO‐7M. 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 × 10‐4M. 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.