Regulation of pendrin by cAMP: possible involvement in β-adrenergic-dependent NaCl retention
Regulation of pendrin by cAMP: possible involvement in β-adrenergic-dependent NaCl retention
复制标题
DOI：
10.1152/ajprenal.00403.2011
复制
发表时间：
2012-05-01
影响因子：
4.2
通讯作者：
Doucet, Alain
中科院分区：
文献类型：
--
作者：
Azroyan, Anie;Morla, Luciana;Doucet, Alain
[10]李文辉，李文辉.环磷酸腺苷对pendrin的调节：可能参与β肾上腺素能依赖性NaCl潴留。美国肾脏生理学杂志302：F1180-F1187，2012年。首次发表于2012年1月18日; doi：10.1152/ajprenal.00403.2011。钠依赖性阴离子交换剂pendrin在包括肾皮质集合管（CCD）在内的几种组织中表达，在那里它充当氯离子/碳酸氢根交换剂，并且已显示参与酸碱平衡和血压的调节。已知肾交感神经系统在盐诱导的高血压的发展中起关键作用。本研究旨在确定pendrin是否可能部分介导β肾上腺素能受体（β-AR）对肾脏盐处理的影响。我们研究了pendrin活性的cAMP/蛋白激酶A（PKA）信号通路的调节，无论是在体外稳定转染pendrin cDNA的负鼠肾近端（OKP）细胞和离体分离的微灌注CCD异丙肾上腺素，β-AR激动剂刺激。我们发现，OKP细胞中cAMP/PKA通路的刺激增加了细胞表面pendrin的量以及其转运活性。这些作用源于pendrin的胞吐增加，并与其磷酸化有关。此外，cAMP对pendrin的膜表达和活性的影响被废除，通过突变位于pendrin的细胞内N-末端结构域的丝氨酸49。最后，我们发现，异丙肾上腺素增加pendrin贩运顶端膜以及重吸收的Cl-和Na+在微灌注CCD。总之，我们的研究结果强烈表明，pendrin激活cAMP/PKA途径的基础异丙肾上腺素诱导的刺激NaCl在肾脏集合管的重吸收，一种机制可能参与钠保留β-肾上腺素能受体激动剂的作用。
Azroyan A, Morla L, Crambert G, Laghmani K, Ramakrishnan S, Edwards A, Doucet A. Regulation of pendrin by cAMP: possible involvement in beta-adrenergic-dependent NaCl retention. Am J Physiol Renal Physiol 302: F1180-F1187, 2012. First published January 18, 2012; doi:10.1152/ajprenal.00403.2011.-The sodium-in-dependent anion exchanger pendrin is expressed in several tissues including the kidney cortical collecting duct (CCD), where it acts as a chloride/bicarbonate exchanger and has been shown to participate in the regulation of acid-base homeostasis and blood pressure. The renal sympathetic nervous system is known to play a key role in the development of salt-induced hypertension. This study aimed to determine whether pendrin may partly mediate the effects of beta adrenergic receptors (beta-AR) on renal salt handling. We investigated the regulation of pendrin activity by the cAMP/protein kinase A (PKA) signaling pathway, both in vitro in opossum kidney proximal (OKP) cells stably transfected with pendrin cDNA and ex vivo in isolated microperfused CCDs stimulated by isoproterenol, a beta-AR agonist. We found that stimulation of the cAMP/PKA pathway in OKP cells increased the amount of pendrin at the cell surface as well as its transport activity. These effects stemmed from increased exocytosis of pendrin and were associated with its phosphorylation. Furthermore, cAMP effects on the membrane expression and activity of pendrin were abolished by mutating the serine 49 located in the intracellular N-terminal domain of pendrin. Finally, we showed that isoproterenol increases pendrin trafficking to the apical membrane as well as the reabsorption of both Cl- and Na+ in microperfused CCDs. All together, our results strongly suggest that pendrin activation by the cAMP/PKA pathway underlies isoproterenol-induced stimulation of NaCl reabsorption in the kidney collecting duct, a mechanism likely involved in the sodium-retaining effect of beta-adrenergic agonists.