Duerson K, White R E, Jiang F, Schonbrunn A, Armstrong D L
Laboratory of Cellular & Molecular Pharmacology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Neuropharmacology. 1996;35(7):949-61. doi: 10.1016/0028-3908(96)00131-1.
The stimulation of large-conductance, calcium-activated (BK) potassium channels by somatostatin through protein dephosphorylation in rat pituitary tumor cells (White et al., Nature 351, 570-573, 1991) is blocked by drugs that interfere with arachidonic acid release by phospholipase A2 and metabolism by 5-lip-oxygenase. In contrast, higher concentrations of the same drugs had no effect on BK channel gating in cell-free patches, on the inhibition of adenylyl cyclase by somatostatin, or on the stimulation of BK channels by protein dephosphorylation through a cGMP-dependent pathway (White et al., Nature 361, 263-266, 1993). Exogenous arachidonic acid (1-20 muM) stimulated BK channel activity through protein dephosphorylation as effectively as somatostatin and was also blocked by inhibitors of lipoxygenases but not by inhibitors of phospholipase A2. These results support the hypothesis that lipoxygenase metabolites of arachidonic acid are second messengers linking pertussis toxin sensitive G-proteins to protein phosphatases regulating potassium channel activity (Armstrong and White, Trends Neurosci. 15, 403-408, 1992).
生长抑素通过大鼠垂体瘤细胞中的蛋白质去磷酸化作用对大电导钙激活（BK）钾通道的刺激（怀特等人，《自然》351卷，570 - 573页，1991年）被干扰磷脂酶A2释放花生四烯酸以及5 - 脂氧合酶代谢的药物所阻断。相比之下，相同药物的较高浓度对无细胞膜片中BK通道的门控、生长抑素对腺苷酸环化酶的抑制作用或通过cGMP依赖性途径的蛋白质去磷酸化对BK通道的刺激均无影响（怀特等人，《自然》361卷，263 - 266页，1993年）。外源性花生四烯酸（1 - 20微摩尔）通过蛋白质去磷酸化作用刺激BK通道活性的效果与生长抑素相同，并且也被脂氧合酶抑制剂所阻断，但不被磷脂酶A2抑制剂所阻断。这些结果支持了这样一种假说，即花生四烯酸的脂氧合酶代谢产物是将百日咳毒素敏感的G蛋白与调节钾通道活性的蛋白质磷酸酶联系起来的第二信使（阿姆斯特朗和怀特，《神经科学趋势》15卷，403 - 408页，1992年）。
