Brain mineralocorticoid receptors and centrally regulated functions
Brain mineralocorticoid receptors and centrally regulated functions
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DOI：
10.1046/j.1523-1755.2000.00971.x
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发表时间：
2000-04-01
影响因子：
19.6
通讯作者：
de Jong, W
中科院分区：
文献类型：
--
作者：
de Kloet, ER;van Acker, SABE;de Jong, W
盐皮质激素受体(MRS)表达于边缘神经元，尤其是海马神经元，既保留醛固酮，又保留皮质酮。皮质酮的基础浓度已经基本上占据了边缘MR类型，这表明在海马神经元中，MR活动而不是配体的生物利用度是速率限制的。脑室周围区域表达参与盐平衡控制的MRS，由于存在11β-羟基类固醇脱氢酶，因此对醛固酮具有选择性。MR位于海马CA1、CA2和齿状回，与糖皮质激素受体(GRs)共定位。这两种受体以协调的方式调节皮质酮在信息处理中的作用，皮质酮对行为适应和相关的神经内分泌反应是至关重要的。MRS在主动模式下工作，决定应激反应系统的敏感性，而GRs在反应性模式下促进应激恢复。在神经元水平上，MR介导的活动维持稳定的兴奋性音调，并减弱调制信号的影响。相反，GR介导的效应抑制了兴奋性刺激短暂提高的兴奋性。MR还参与控制自主流出和音量调节。MR拮抗剂的效果证明了这一点，因为MDR P-糖蛋白阻碍了合成类固醇进入大脑。MR拮抗剂可减弱对应激源的压力反应，例如在尾部脉搏图中所经历的反应。MR拮抗剂后利尿和尿液电解质排泄增加，但在双侧肾失神经后这种作用消失。目前尚不清楚MR对中枢心血管调节的这些方面的影响发生在哪些脑细胞。
Mineralocorticoid receptors (MRs) expressed in limbic neurons, notably of hippocampus, retain both aldosterone and corticosterone. Basal concentrations of corticosterone already substantially occupy the limbic MR type, suggesting that in hippocampal neurons, MR activity rather than ligand bioavailability is rate limiting. The periventricular region expresses MRs involved in the control of salt homeostasis, which are aldosterone selective because of the presence of 11 beta-hydroxy-steroid dehydrogenase. MR is in hippocampal CA1, CA2, and dentate gyrus colocalized with glucocorticoid receptors (GRs). Both receptor types mediate in a coordinate manner the corticosterone action on information processing critical for behavioral adaptation and associated neuroendocrine responses to stress. MRs operate in proactive mode determining the sensitivity of the stress response system, while GRs facilitate recovery from stress in reactive mode. On the neuronal level, MR-mediated action maintains a stable excitatory tone and attenuates the influence of modulatory signals. In contrast, GR-mediated effects suppress excitability transiently raised by excitatory stimuli. MR is also involved in control of autonomic outflow and volume regulation. This was demonstrated by the effect of an MR antagonist, which was administered centrally, because mdr P-glycoproteins hamper the access of synthetic steroids to the brain. The MR antagonist attenuates presser responses to a stressor, such as experienced during tail sphygmography. Diuresis and urinary electrolyte excretion are increased after the MR antagonist, but this effect is abolished after bilateral denervation of the kidney. It is presently unknown in which brain cells the MR-mediated effects on these aspects of central cardiovascular regulation occur.