Yang Zhiwei, Asico Laureano D, Yu Peiying, Wang Zheng, Jones John E, Escano Crisanto S, Wang Xiaoyan, Quinn Mark T, Sibley David R, Romero Guillermo G, Felder Robin A, Jose Pedro A
Department of Pediatrics and Physiology, Georgetown University Medical Center, 3800 Reservoir Rd., NW, Washington, DC 20007, USA.
Am J Physiol Regul Integr Comp Physiol. 2006 Jan;290(1):R96-R104. doi: 10.1152/ajpregu.00434.2005.
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.
D1样受体（D1和/或D5）的激活可诱导抗氧化反应；然而，其抗氧化作用所涉及的机制尚不清楚。我们推测，D5受体的刺激会抑制NADPH氧化酶活性，从而减少活性氧（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-/-小鼠肾脏和大脑中的NADPH氧化酶蛋白表达（gp91(phox)、p47(phox)和Nox 4）及活性，以及血浆硫代巴比妥酸反应性物质（TBARS）均高于D5+/+小鼠。此外，NADPH氧化酶抑制剂阿朴吗啡使D5-/-小鼠的血压、肾脏NADPH氧化酶活性和血浆TBARS恢复正常。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了NADPH氧化酶活性、其一个亚基（gp91(phox)）的表达及ROS的产生。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产生的能力可能部分解释了D5受体激活的降压作用。
