Arachidonic acid inhibits myosin light chain phosphatase and sensitizes smooth muscle to calcium.
Arachidonic acid inhibits myosin light chain phosphatase and sensitizes smooth muscle to calcium.
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DOI：
10.1016/s0021-9258(19)36636-0
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发表时间：
1992-10
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影响因子：
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通讯作者：
Ming C. Gong;Annette FuglsangSlI;Dario Alessill;Sei KobayashiS;Philip Cohenll;Avril V. SomlyoS;A. Somlyo
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文献类型：
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作者：
Ming C. Gong;Annette FuglsangSlI;Dario Alessill;Sei KobayashiS;Philip Cohenll;Avril V. SomlyoS;A. Somlyo
花生四烯酸（AA）增加，在恒定的Ca 2+，力和20 kDa肌球蛋白轻链（MLC 20）的磷酸化透化平滑肌的水平，并减缓松弛和MLC 20去磷酸化。AA代谢抑制剂（吲哚美辛、去甲二氢愈创木酸或没食子酸丙酯）、蛋白激酶C（假肽）或鸟苷-5 '-O-（β-硫代二磷酸）均不抑制AA的Ca（2+）增敏作用，AA在空气中氧化可消除该作用。一种非代谢的AA类似物，5，8，11，14-二十碳四炔酸）也具有Ca（2+）增敏作用。用皂苷广泛处理可消除佛波醇12，13-二丁酸酯和鸟苷-5 '-O-（γ-硫代三磷酸）的Ca（2+）增敏作用，但不能消除AA的作用。一个纯化的，低聚MLC 20磷酸酶分离肌胃平滑肌被AA分解成亚基，其活性被抑制向重肌球蛋白，但不磷酸化酶。我们的结论是，AA可能作为信使促进蛋白磷酸化，通过直接抑制蛋白磷酸酶的形式，在体内MLC 20去磷酸化。
Arachidonic acid (AA) increased, at constant Ca2+, the levels of force and 20-kDa myosin light chain (MLC20) phosphorylation in permeabilized smooth muscle, and slowed relaxation and MLC20 dephosphorylation. The Ca(2+)-sensitizing effect of AA was not inhibited by inhibitors of AA metabolism (indomethacin, nordihydroguaiaretic acid, or propyl gallate), of protein kinase C (pseudopeptide) or by guanosine-5‘-O-(beta-thiodiphosphate) and was abolished by oxidation of AA in air. A non-metabolizable AA analog, 5,8,11,14-eicosatetraynoic acid) also had Ca(2+)-sensitizing effects. Extensive treatment with saponin abolished the Ca(2+)-sensitizing effects of phorbol 12,13-dibutyrate and guanosine-5‘-O-(gamma-thiotriphosphate), but not that of AA. A purified, oligomeric MLC20 phosphatase isolated from gizzard smooth muscle was dissociated into subunits by AA, and its activity was inhibited toward heavy meromyosin but not phosphorylase. We conclude that AA may act as a messenger-promoting protein phosphorylation through direct inhibition of the form of protein phosphatase(s) that dephosphorylate MLC20 in vivo.