Kitamura K, Houchi H, Yoshizumi M, Matsumoto K, Oka M
Department of Neurosurgery, School of Medicine, University of Tokushima, Japan.
Tokushima J Exp Med. 1996 Jun;43(1-2):17-23.
The effects of small-conductance Ca2(+)-activated K+ channel (SK channel) blocker, apamin, on histamine-stimulated catecholamine biosynthesis and tyrosine hydroxylase phosphorylation in cultured bovine adrenal chromaffin cells were investigated. Histamine (10(-10)-10(-6) M) stimulated [14C]catecholamine biosynthesis from [14C]tyrosine (but not from [14C]DOPA). Apamin (10(-6) M) enhanced the histamine-stimulated catecholamine biosynthesis, which was abolished by omission of extracellular Ca2+. Histamine increased the intracellular free Ca2+ concentration ([Ca2+]i), and this increased [Ca2+]i was potentiated by the presence of apamin. The increase in histamine-stimulated catecholamine biosynthesis with apamin was sensitive to the inhibitors of protein kinase C and Ca2+/calmodulin dependent protein kinase. Apamin increased the histamine-induced phosphorylation of tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis. These results suggest that in cultured bovine adrenal chromaffin cells the inhibition of SK channel results in potentiation of catecholamine biosynthesis and tyrosine hydroxylase phosphorylation induced by histamine and that these stimulatory effects may result from the activation of protein kinase C and Ca2+/calmodulin-dependent protein kinase through an increase in [Ca2+]i.
研究了小电导Ca2+激活的K+通道（SK通道）阻滞剂蜂毒明肽对培养的牛肾上腺嗜铬细胞中组胺刺激的儿茶酚胺生物合成及酪氨酸羟化酶磷酸化的影响。组胺（10^(-10)-10^(-6) M）刺激了[14C]酪氨酸生成[14C]儿茶酚胺的生物合成（但不刺激[14C]多巴生成儿茶酚胺）。蜂毒明肽（10^(-6) M）增强了组胺刺激的儿茶酚胺生物合成，而去除细胞外Ca2+可消除这种增强作用。组胺增加了细胞内游离Ca2+浓度（[Ca2+]i），并且蜂毒明肽的存在增强了这种升高的[Ca2+]i。蜂毒明肽使组胺刺激的儿茶酚胺生物合成增加，这对蛋白激酶C和Ca2+/钙调蛋白依赖性蛋白激酶的抑制剂敏感。蜂毒明肽增加了组胺诱导的酪氨酸羟化酶磷酸化，酪氨酸羟化酶是儿茶酚胺生物合成中的限速酶。这些结果表明，在培养的牛肾上腺嗜铬细胞中，SK通道的抑制导致组胺诱导的儿茶酚胺生物合成和酪氨酸羟化酶磷酸化增强，并且这些刺激作用可能是通过[Ca2+]i的增加激活蛋白激酶C和Ca2+/钙调蛋白依赖性蛋白激酶所致。
