D5 dopamine receptor regulation of reactive oxygen species production, NADPH oxidase, and blood pressure.
D5 dopamine receptor regulation of reactive oxygen species production, NADPH oxidase, and blood pressure.
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DOI：
10.1152/ajpregu.00434.2005
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发表时间：
2006
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影响因子：
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通讯作者：
Zhiwei Yang;L. Asico;P. Yu;Z. Wang;J. Jones;C. Escano;Xiaoyan Wang;M. Quinn;D. Sibley;G. R
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作者：
Zhiwei Yang;L. Asico;P. Yu;Z. Wang;J. Jones;C. Escano;Xiaoyan Wang;M. Quinn;D. Sibley;G. R
D1样受体（D1和/或D5）的激活诱导抗氧化反应;然而，其抗氧化作用的机制尚不清楚。我们假设D5受体的刺激抑制NADPH氧化酶活性，从而抑制活性氧（ROS）的产生。我们在D5受体缺陷（D5-/-）和野生型（D5+/+）小鼠中研究了这个问题。D5-/-小鼠的肾脏和大脑中NADPH氧化酶蛋白表达（gp 91（phox）、p47（phox）和Nox 4）和活性以及血浆硫代巴比妥酸反应物质（TBARS）均高于D5+/+小鼠。此外，在D5-/-小鼠中，夹竹桃麻素（NADPH氧化酶抑制剂）使血压、肾NADPH氧化酶活性和血浆TBARS正常化。在异源表达人D5受体的HEK-293细胞中，其激动剂非诺多泮降低NADPH氧化酶活性、其亚基之一（gp 91（phox））的表达和ROS产生。D5受体激活对NADPH氧化酶活性的抑制作用不依赖于cAMP/PKA，但部分依赖于磷脂酶D2。D5受体刺激减少ROS产生的能力可以部分解释D5受体激活的抗高血压作用。
Activation of D1-like receptors (D1 and/or D5) induces antioxidant responses; however, the mechanism(s) involved in their antioxidant actions are not known. We hypothesized that stimulation of the D5 receptor inhibits NADPH oxidase activity, and thus the production of reactive oxygen species (ROS). We investigated this issue in D5 receptor-deficient (D5-/-) and wild-type (D5+/+) mice. NADPH oxidase protein expression (gp91(phox), p47(phox), and Nox 4) and activity in kidney and brain, as well as plasma thiobarbituric acid-reactive substances (TBARS) were higher in D5-/- than in D5+/+ mice. Furthermore, apocynin, an NADPH oxidase inhibitor, normalized blood pressure, renal NADPH oxidase activity, and plasma TBARS in D5-/- mice. In HEK-293 cells that heterologously expressed human D5 receptor, its agonist fenoldopam decreased NADPH oxidase activity, expression of one of its subunits (gp91(phox)), and ROS production. The inhibitory effect of the D5 receptor activation on NADPH oxidase activity was independent of cAMP/PKA but was partially dependent on phospholipase D2. The ability of D5 receptor stimulation to decrease ROS production may explain, in part, the antihypertensive action of D5 receptor activation.