Linden David R, el-Fakahany Esam E
Division of Neuroscience Research in Psychiatry, University of Minnesota, Minneapolis, Minnesota, USA.
Neurochem Res. 2002 Jun;27(6):441-9. doi: 10.1023/a:1019892700049.
Strong evidence supports that nitric oxide (NO) alters cell signaling pathways involving arachidonic acid (AA). Little is known, however, about the reciprocal modulation of nitrergic pathways by AA. The effects of exogenous AA on signal transduction of M1 muscarinic acetylcholine receptors were investigated in a model system of stably transfected Chinese hamster ovary cells. AA concentration-dependently inhibited the effects of carbachol in producing NO (IC50 = 191 microM) but did not alter inositol phosphate production or M1 receptor binding. AA inhibited both carbachol-induced transient and sustained increase in intracellular calcium concentration ([Ca2+]i; IC50 = 11 and 12 microM, respectively). Furthermore, AA-induced increase in [Ca2+]i cross-desensitizes with thapsigargin, but AA does not inhibit Ca(2+)-ATPase activity. These data support the concept that AA concentration-dependently inhibits receptor-mediated NO production at the level of calcium mobilization.
有力证据支持一氧化氮（NO）会改变涉及花生四烯酸（AA）的细胞信号通路。然而，关于AA对硝化能通路的反向调节作用却知之甚少。在稳定转染的中国仓鼠卵巢细胞模型系统中，研究了外源性AA对M1毒蕈碱型乙酰胆碱受体信号转导的影响。AA浓度依赖性地抑制卡巴胆碱产生NO的作用（IC50 = 191 microM），但不改变肌醇磷酸的产生或M1受体结合。AA抑制卡巴胆碱诱导的细胞内钙浓度（[Ca2+]i）的瞬时和持续升高（IC50分别为11和12 microM）。此外，AA诱导的[Ca2+]i升高与毒胡萝卜素交叉脱敏，但AA不抑制Ca(2+)-ATP酶活性。这些数据支持这样的概念，即AA在钙动员水平上浓度依赖性地抑制受体介导的NO产生。
