Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, J. B. Winslowsvej 21, 3, 5000, Odense C, Denmark.
Pflugers Arch. 2013 Jan;465(1):25-37. doi: 10.1007/s00424-012-1126-7. Epub 2012 Jun 26.
A major rate-limiting step in the renin-angiotensin-aldosterone system is the release of active renin from endocrine cells (juxtaglomerular (JG) cells) in the media layer of the afferent glomerular arterioles. The number and distribution of JG cells vary with age and the physiological level of stimulation; fetal life and chronic stimulation by extracellular volume contraction is associated with recruitment of renin-producing cells. Upon stimulation of renin release, labeled renin granules "disappear;" the number of granules decrease; cell membrane surface area increases in single cells, and release is quantal. Together, this indicates exocytosis as the predominant mode of release. JG cells release few percent of total renin content by physiological stimulation, and recruitment of renin cells is preferred to recruitment of granules during prolonged stimulation. Several endocrine and paracrine agonists, neurotransmitters, and cell swelling converge on the stimulatory cyclic AMP (cAMP) pathway. Renin secretion is attenuated in mice deficient in beta-adrenoceptors, prostaglandin E(2)-EP4 receptors, Gsα protein, and adenylyl cyclases 5 and 6. Phosphodiesterases (PDE) 3 and 4 degrade cAMP in JG cells, and PDE3 is inhibited by cyclic GMP (cGMP) and couples the cGMP pathway to the cAMP pathway. Cyclic AMP enhances K(+)-current in JG cells and is permissive for secretion by stabilizing membrane potential far from threshold that activates L-type voltage-gated calcium channels. Intracellular calcium paradoxically inhibits renin secretion likely through attenuated formation and enhanced degradation of cAMP; by activation of chloride currents and interaction with calcineurin. Connexin 40 is necessary for localization of JG cells in the vascular wall and for pressure- and macula densa-dependent suppression of renin release.
肾素-血管紧张素-醛固酮系统中的一个主要限速步骤是内分泌细胞（肾小球旁细胞）从入球小动脉血管中层释放有活性的肾素。肾小球旁细胞的数量和分布随年龄和生理刺激水平而变化；胎儿期和细胞外液体积收缩的慢性刺激与产生肾素的细胞的募集有关。在肾素释放受到刺激时，标记的肾素颗粒“消失”；颗粒数量减少；单个细胞的细胞膜表面积增加，并且释放是量子化的。总的来说，这表明胞吐作用是主要的释放方式。在生理刺激下，肾小球旁细胞通过胞吐作用释放的肾素仅占总肾素含量的一小部分，并且在长时间刺激时，优先募集肾素细胞而不是募集颗粒。几种内分泌和旁分泌激动剂、神经递质和细胞肿胀都集中在刺激环磷酸腺苷（cAMP）途径上。缺乏β-肾上腺素能受体、前列腺素 E2-EP4 受体、Gsα 蛋白和腺苷酸环化酶 5 和 6 的小鼠，肾素分泌会减弱。磷酸二酯酶（PDE）3 和 4 在肾小球旁细胞中降解 cAMP，PDE3 被环鸟苷酸（cGMP）抑制，并将 cGMP 途径与 cAMP 途径偶联。cAMP 增强肾小球旁细胞中的 K+电流，并通过稳定远离激活 L 型电压门控钙通道的膜电位来促进分泌。细胞内钙出人意料地抑制肾素分泌，可能是通过减弱 cAMP 的形成和增强降解；通过激活氯离子电流和与钙调神经磷酸酶相互作用。连接蛋白 40 是将肾小球旁细胞定位于血管壁中和对压力和致密斑依赖性肾素释放的抑制所必需的。
