Spät András, Hunyady László
Dept. of Physiology, Semmelweis University, Faculty of Medicine, PO Box 259, H-1444 Budapest, Hungary.
Physiol Rev. 2004 Apr;84(2):489-539. doi: 10.1152/physrev.00030.2003.
Aldosterone secretion by glomerulosa cells is stimulated by angiotensin II (ANG II), extracellular K(+), corticotrophin, and several paracrine factors. Electrophysiological, fluorimetric, and molecular biological techniques have significantly clarified the molecular action of these stimuli. The steroidogenic effect of corticotrophin is mediated by adenylyl cyclase, whereas potassium activates voltage-operated Ca(2+) channels. ANG II, bound to AT(1) receptors, acts through the inositol 1,4,5-trisphosphate (IP(3))-Ca(2+)/calmodulin system. All three types of IP(3) receptors are coexpressed, rendering a complex control of Ca(2+) release possible. Ca(2+) release is followed by both capacitative and voltage-activated Ca(2+) influx. ANG II inhibits the background K(+) channel TASK and Na(+)-K(+)-ATPase, and the ensuing depolarization activates T-type (Ca(v)3.2) Ca(2+) channels. Activation of protein kinase C by diacylglycerol (DAG) inhibits aldosterone production, whereas the arachidonate released from DAG in ANG II-stimulated cells is converted by lipoxygenase to 12-hydroxyeicosatetraenoic acid, which may also induce Ca(2+) signaling. Feedback effects and cross-talk of signal-transducing pathways sensitize glomerulosa cells to low-intensity stimuli, such as physiological elevations of [K(+)] (< or =1 mM), ANG II, and ACTH. Ca(2+) signaling is also modified by cell swelling, as well as receptor desensitization, resensitization, and downregulation. Long-term regulation of glomerulosa cells involves cell growth and proliferation and induction of steroidogenic enzymes. Ca(2+), receptor, and nonreceptor tyrosine kinases and mitogen-activated kinases participate in these processes. Ca(2+)- and cAMP-dependent phosphorylation induce the transfer of the steroid precursor cholesterol from the cytoplasm to the inner mitochondrial membrane. Ca(2+) signaling, transferred into the mitochondria, stimulates the reduction of pyridine nucleotides.
球状带细胞分泌醛固酮受到血管紧张素 II（ANG II）、细胞外钾离子（K⁺）、促肾上腺皮质激素以及几种旁分泌因子的刺激。电生理学、荧光测定法和分子生物学技术已显著阐明了这些刺激的分子作用。促肾上腺皮质激素的类固醇生成作用由腺苷酸环化酶介导，而钾离子激活电压门控性钙通道。与 AT₁ 受体结合的 ANG II 通过肌醇 1,4,5 - 三磷酸（IP₃）- 钙/钙调蛋白系统发挥作用。三种类型的 IP₃ 受体均共表达，使得对钙释放进行复杂调控成为可能。钙释放之后是容量性和电压激活的钙内流。ANG II 抑制背景钾通道 TASK 和钠钾 ATP 酶，随后的去极化激活 T 型（Ca(v)3.2）钙通道。二酰基甘油（DAG）激活蛋白激酶 C 会抑制醛固酮生成，而在 ANG II 刺激的细胞中从 DAG 释放的花生四烯酸被脂氧合酶转化为 12 - 羟基二十碳四烯酸，其也可能诱导钙信号传导。信号转导通路的反馈效应和相互作用使球状带细胞对低强度刺激敏感，如生理水平升高的[K⁺]（≤1 mM）、ANG II 和促肾上腺皮质激素。钙信号也会因细胞肿胀以及受体脱敏、再敏化和下调而发生改变。球状带细胞的长期调节涉及细胞生长、增殖以及类固醇生成酶的诱导。钙、受体和非受体酪氨酸激酶以及丝裂原活化激酶参与这些过程。钙和 cAMP 依赖性磷酸化诱导类固醇前体胆固醇从细胞质转移至线粒体内膜。传入线粒体的钙信号刺激吡啶核苷酸的还原。
