Rocco S, Ambroz C, Aguilera G
Section on Endocrine Physiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
Endocrinology. 1990 Dec;127(6):3103-10. doi: 10.1210/endo-127-6-3103.
Although serotonin (5HT) is a recognized stimulator of aldosterone secretion in vivo and in vitro, its physiological role as a regulator of mineralocorticoid secretion and its mechanism of action in the adrenal glomerulosa have not been elucidated. To address these questions we studied the interaction of 5HT with other aldosterone regulators in isolated rat adrenal glomerulosa cells. 5HT stimulated aldosterone production 14-fold, with an ED50 of 20 +/- 5 nM, and stimulation was maximal at 0.8 microM. The stimulation of aldosterone production by 5HT was accompanied by a 5-fold increase in cAMP production, with an ED50 of 1 microM. Threshold levels of 5HT (1 nM) potentiated the effect of submaximal concentrations of angiotensin-II (AII), decreasing the ED50 from 1.3 to 0.46 nM and increasing the maximum response in an additive manner. In contrast, the stimulatory effect of 5HT was purely additive to that of submaximal ACTH concentrations. 5HT had no effect on aldosterone secretion stimulated by maximal ACTH concentrations, despite full additivity on cAMP accumulation. Stimulations of steroidogenesis by potassium and 5HT were fully additive at submaximal concentrations, but only partially additive at-maximal levels. To determine the mechanism of the synergistic effects of AII and 5HT, we analyzed the interaction of both stimuli on cAMP accumulation, intracellular calcium, and inositol phosphate formation. Consistent with the inhibitory effect of AII on adenylate cyclase, in the presence of AII the stimulation of cAMP by 5HT was reduced by 18 +/- 3%. 5HT alone had no effect on cytosolic calcium, but significantly enhanced the peak and later phases of the AII-stimulated increase (P less than 0.005). This effect of 5HT was due to calcium influx and not to release from intracellular pools, as shown by suppression of the potentiation in the absence of extracellular calcium and the lack of effect of 5HT on basal or AII-stimulated inositol phosphate formation. The ability of low concentrations of 5HT to potentiate the stimulatory effect of AII on aldosterone secretion suggests that under some physiological conditions, 5HT may play a role in regulating the adrenal sensitivity to AII.
尽管血清素（5HT）在体内和体外都是公认的醛固酮分泌刺激剂，但其作为盐皮质激素分泌调节剂的生理作用及其在肾上腺球状带中的作用机制尚未阐明。为了解决这些问题，我们研究了5HT与分离的大鼠肾上腺球状带细胞中其他醛固酮调节剂的相互作用。5HT刺激醛固酮生成增加14倍，半数有效剂量（ED50）为20±5 nM，在0.8 microM时刺激作用最大。5HT刺激醛固酮生成伴随着cAMP生成增加5倍，ED50为1 microM。5HT的阈值水平（1 nM）增强了次最大浓度血管紧张素-II（AII）的作用，将ED50从1.3 nM降至0.46 nM，并以相加方式增加最大反应。相反，5HT的刺激作用与次最大浓度促肾上腺皮质激素（ACTH）的刺激作用完全相加。尽管对cAMP积累完全相加，但5HT对最大ACTH浓度刺激的醛固酮分泌没有影响。在次最大浓度下，钾和5HT对类固醇生成的刺激作用完全相加，但在最大水平时仅部分相加。为了确定AII和5HT协同作用的机制，我们分析了两种刺激对cAMP积累、细胞内钙和肌醇磷酸形成的相互作用。与AII对腺苷酸环化酶的抑制作用一致，在存在AII的情况下，5HT对cAMP的刺激作用降低了18±3%。单独的5HT对细胞质钙没有影响，但显著增强了AII刺激增加的峰值和后期阶段（P<0.005）。5HT的这种作用是由于钙内流，而不是从细胞内储存库释放，这通过在无细胞外钙时抑制增强作用以及5HT对基础或AII刺激的肌醇磷酸形成无影响得以证明。低浓度5HT增强AII对醛固酮分泌刺激作用的能力表明，在某些生理条件下，5HT可能在调节肾上腺对AII的敏感性中发挥作用。
