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>Differential down-regulation of protein kinase C selectively affects IgE-dependent exocytosis and inositol trisphosphate formation
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Differential down-regulation of protein kinase C selectively affects IgE-dependent exocytosis and inositol trisphosphate formation
pShort-term treatment of rat basophilic leukaemia (RBL-2H3) cells with the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) activates protein kinase C (PKC) and results in the inhibition of the IgE-dependent formation of inositol phosphates, but in the potentiation of serotonin secretion. Long-term treatment with TPA, which depletes the cells of their endogenous PKC, eliminates both Ca2(+)-ionophore- and TPA- as well as IgE-dependent secretion, but it potentiates by 1.7-fold IgE-induced inositol phosphate formation. Taken together, these observations strongly suggest that the dual actions of TPA on IgE-dependent responses are both mediated by PKC. The opposing effects of TPA are differentially down-regulated. Following TPA treatment, the rate by which the cells lose their ability to undergo exocytosis is faster than the rate at which inhibition of inositol phosphates formation is relieved and their production potentiated. In addition, both processes show different sensitivities to inhibitors of PKC action. Whereas IgE-dependent secretion is completely blocked by the PKC inhibitors K252a, H-7 and sphingosine [concns. causing 50% inhibition (IC50 values) = 25 ng/ml 80 microns and 30 microns respectively], these inhibitors do not relieve inhibition of inositol phosphate formation by TPA, nor do they potentiate this response. These results may imply that the bidirectional control exerted by PKC on IgE-dependent responses is mediated by its different isoenzymes./p
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机译：>用佛波醇酯12-O-十四烷酰佛波醇13-乙酸酯（TPA）短期治疗大鼠嗜碱性白血病（RBL-2H3）细胞可激活蛋白激酶C（PKC），并抑制IgE依赖性形成肌醇磷酸，但在5-羟色胺分泌增强。用TPA长期治疗可消除其内源性PKC细胞，消除Ca2（+）-离子载体和TPA-以及IgE依赖的分泌，但可通过1.7倍IgE诱导的肌醇磷酸形成而增强作用。综上所述，这些观察结果强烈表明，TPA对IgE依赖性应答的双重作用均由PKC介导。 TPA的相反作用被不同地下调。在TPA处理后，细胞丧失其胞吐能力的速率比减轻肌醇磷酸酯形成抑制作用和增强其产生的速率要快。另外，两种方法均显示出对PKC作用抑制剂的不同敏感性。 IgE依赖的分泌完全被PKC抑制剂K252a，H-7和鞘氨醇[concns。分别引起50％抑制（IC50值）= 25 ng / ml 80微米和30微米]，这些抑制剂不能缓解TPA对肌醇磷酸酯形成的抑制作用，也不能增强这种反应。这些结果可能暗示PKC对IgE依赖性反应的双向控制是由其不同的同工酶介导的。
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