Wakade A R, Malhotra R K, Wakade T D
Nature. 1986;321(6071):698-700. doi: 10.1038/321698a0.
Several investigators have shown that tumour promoter phorbol esters mimic the effects of endogenous diacylglycerol to activate a second messenger, protein kinase C. These phorbol esters have proved to be valuable tools for exploring the role of protein kinase C in many cellular functions. We demonstrate here that secretion of catecholamines evoked from the rat adrenal gland by stimulation of splanchnic nerves, excess potassium (K+) and nicotine is facilitated by phorbol 12,13-dibutyrate. An inhibitor of protein kinase C, polymixin B, produced concentration-dependent inhibition of the evoked secretion, and the effect was reversed by the phorbol ester. Furthermore, we show that an increase in the accumulation of radioactively labelled calcium (45Ca) obtained in the adrenal medulla after stimulation with nicotinic agonists and excess K+ is further enhanced by phorbol ester. Muscarine-evoked secretion of catecholamines, which depends on mobilization of intracellularly bound Ca2+, was not associated with an increase in 45Ca2+ uptake, and phorbol ester did not facilitate either catecholamine secretion or 45Ca2+ accumulation. We suggest that protein kinase C is involved in the exocytotic secretion of catecholamines by regulating the influx of Ca2+ through voltage-sensitive and nicotine receptor-linked Ca2+ channels of rat chromaffin cells.
几位研究者已表明，肿瘤促进剂佛波酯可模拟内源性二酰甘油的作用来激活第二信使蛋白激酶C。这些佛波酯已被证明是探索蛋白激酶C在许多细胞功能中作用的有价值工具。我们在此证明，佛波酯可促进由刺激内脏神经、过量钾（K+）和尼古丁引起的大鼠肾上腺儿茶酚胺分泌。蛋白激酶C的抑制剂多粘菌素B对诱发分泌产生浓度依赖性抑制，且该作用可被佛波酯逆转。此外，我们表明，在用烟碱激动剂和过量K+刺激后，肾上腺髓质中放射性标记钙（45Ca）积累的增加会被佛波酯进一步增强。毒蕈碱诱发的儿茶酚胺分泌依赖于细胞内结合钙（Ca2+）的动员，与45Ca2+摄取增加无关，且佛波酯既不促进儿茶酚胺分泌也不促进45Ca2+积累。我们认为蛋白激酶C通过调节Ca2+通过大鼠嗜铬细胞的电压敏感性和烟碱受体连接的Ca2+通道的内流，参与儿茶酚胺的胞吐分泌。
