Dopamine and G protein-coupled receptor kinase 4 in the kidney: role in blood pressure regulation.
Dopamine and G protein-coupled receptor kinase 4 in the kidney: role in blood pressure regulation.
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DOI：
10.1016/j.bbadis.2010.02.004
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发表时间：
2010-12
影响因子：
6.2
通讯作者：
Felder, Robin A.
中科院分区：
文献类型：
--
作者：
Jose, Pedro A.;Soares-da-Silva, Patricio;Eisner, Gilbert M.;Felder, Robin A.
关键词：
基因和环境之间复杂的相互作用会导致钠引起的血压（盐敏感性）和/或高血压升高，从而导致显着的发病率和死亡率，影响全球多达 25% 的中年成年人口。由于涉及许多相互作用的系统，确定遗传和/或环境引起的高血压的病因一直很困难。两条主要途径被认为是血压的主要决定因素，因为它们位于肾脏（负责血压调节的关键器官），并且对钠平衡具有深远影响：多巴胺能系统和肾素血管紧张素系统。这些系统相互抵消或调节，与许多细胞内第二信使途径协同调节钠和水的平衡。特别是，G 蛋白偶联受体激酶 4 型 (GRK4) 似乎在调节多巴胺能介导的尿钠排泄中发挥着关键作用。组成型激活的GRK4基因变异体（R65L、A142V和A486V）本身或通过它们与参与血压调节的其他基因的相互作用，与几个种族群体中的原发性高血压和/或盐敏感性高血压相关。 GRK4γ 142V 转基因小鼠在正常盐摄入量下会出现高血压，而 GRK4γ 486V 转基因小鼠仅在盐摄入量增加时才会出现高血压。 GRK4 基因变体已被证明可以使多巴胺受体家族的两个成员 D1 (D1R) 和 D3 (D3R) 多巴胺受体过度磷酸化、脱敏和内化，而且还能增加肾素-血管紧张素系统的关键受体 - 血管紧张素 1 型受体 (AT1R) 的表达。了解涉及血管紧张素和多巴胺的众多血压调节途径可能为钠排泄的药理学调节和最终血压控制提供新的治疗方法。
Complex interactions between genes and environment result in a sodium-induced elevation in blood pressure (salt sensitivity) and/or hypertension that lead to significant morbidity and mortality affecting up to 25% of the middle-aged adult population worldwide. Determining the etiology of genetic and/or environmentally-induced high blood pressure has been difficult because of the many interacting systems involved. Two main pathways have been implicated as principal determinants of blood pressure since they are located in the kidney (the key organ responsible for blood pressure regulation), and have profound effects on sodium balance: the dopaminergic and renin-angiotensin systems. These systems counteract or modulate each other, in concert with a host of intracellular second messenger pathways to regulate sodium and water balance. In particular, the G protein-coupled receptor kinase type 4 (GRK4) appears to play a key role in regulating dopaminergic-mediated natriuresis. Constitutively activated GRK4 gene variants (R65L, A142V, and A486V), by themselves or by their interaction with other genes involved in blood pressure regulation, are associated with essential hypertension and/or salt-sensitive hypertension in several ethnic groups. GRK4γ 142V transgenic mice are hypertensive on normal salt intake while GRK4γ 486V transgenic mice develop hypertension only with an increase in salt intake. GRK4 gene variants have been shown to hyperphosphorylate, desensitize, and internalize two members of the dopamine receptor family, the D1 (D1R) and D3 (D3R) dopamine receptors, but also increase the expression of a key receptor of the renin-angiotensin system, the angiotensin type 1 receptor (AT1R). Knowledge of the numerous blood pressure regulatory pathways involving angiotensin and dopamine may provide new therapeutic approaches to the pharmacological regulation of sodium excretion and ultimately blood pressure control.
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影响因子：
15.9
作者：
ALEXANDER, RW;GILL, JR;KEISER, HR
通讯作者：
KEISER, HR
影响因子：
4.1
作者：
Aveanu, A. S.;Jaquet, P.;Barher, A.
通讯作者：
Barher, A.
非裔美国人中 G 蛋白偶联受体激酶 4 多态性和美托洛尔血压反应：性别特异性和相互作用。
影响因子：
3.2
作者：
Bhatnagar, Vibha;TO'Connor, Daniel;Brophy, Victoria H.;Schork, Nicholas J.;Richard, Erin;Salem, Rany M.;Nievergelt, Caroline M.;Bakris, George L.;Middleton, John P.;Norris, Keith C.;Wright, Jackson;Hiremath, Leena;Contreras, Gabriel;Appel, Lawrence J.;Lipkowitz, Michael S.
通讯作者：
Lipkowitz, Michael S.
影响因子：
4.7
作者：
Abílio, VC;Silva, RH;Frussa-Filho, R
通讯作者：
Frussa-Filho, R
影响因子：
6.1
作者：
Amaral, Joao S.;Pinho, Maria Joao;Soares-da-Silva, Patricio
通讯作者：
Soares-da-Silva, Patricio