Dept. of Medicine, Div. of Nephrology/Hypertension, Univ. of California San Diego and VA San Diego Healthcare System; 3350 La Jolla Village Dr. (9151 San Diego, CA 92161.
Am J Physiol Renal Physiol. 2014 Apr 1;306(7):F701-9. doi: 10.1152/ajprenal.00656.2013. Epub 2014 Jan 29.
Adenylyl cyclases (AC) catalyze formation of cAMP, a critical component of G protein-coupled receptor signaling. So far, nine distinct membrane-bound AC isoforms (AC1-9) and one soluble AC (sAC) have been identified and, except for AC8, all of them are expressed in the kidney. While the role of ACs in renal cAMP formation is well established, we are just beginning to understand the function of individual AC isoforms, particularly with regard to hormonal regulation of transporter and channel phosphorylation, membrane abundance, and trafficking. This review focuses on the role of different AC isoforms in regulating renal water and electrolyte transport in health as well as potential pathological implications of disordered AC isoform function. In particular, we focus on modulation of transporter and channel abundance, activity, and phosphorylation, with an emphasis on studies employing genetically modified animals. As will be described, it is now evident that specific AC isoforms can exert unique effects in the kidney that may have important implications in our understanding of normal physiology as well as disease pathogenesis.
腺苷酸环化酶（AC）催化环磷酸腺苷（cAMP）的形成，这是 G 蛋白偶联受体信号转导的关键组成部分。迄今为止，已经鉴定出 9 种不同的膜结合 AC 同工型（AC1-9）和 1 种可溶性 AC（sAC），除了 AC8 之外，所有这些同工型都在肾脏中表达。虽然 AC 在肾脏 cAMP 形成中的作用已得到充分证实，但我们才刚刚开始了解各个 AC 同工型的功能，特别是在激素调节转运体和通道磷酸化、膜丰度和运输方面。这篇综述重点介绍了不同 AC 同工型在调节肾脏水和电解质转运中的作用，以及 AC 同工型功能紊乱的潜在病理意义。特别是，我们重点关注转运体和通道丰度、活性和磷酸化的调节，强调使用基因修饰动物的研究。正如将描述的那样，现在显然可以看出，特定的 AC 同工型可以在肾脏中发挥独特的作用，这可能对我们理解正常生理学以及疾病发病机制具有重要意义。
