Karten Y J, Stienstra C M, Joëls M
Swammerdam Institute for Life Sciences, University of Amsterdam, 1090 GB Amsterdam, The Netherlands.
J Neuroendocrinol. 2001 Mar;13(3):233-8. doi: 10.1046/j.1365-2826.2001.00616.x.
Granule cells in the rat dentate gyrus contain mineralocorticoid and glucocorticoid receptors to which the adrenal hormone corticosterone binds with differential affinity. These cells also express various receptor-subtypes for serotonin (5-HT), including the 5-HT1A receptor which mediates a membrane hyperpolarization accompanied by a decrease in membrane resistance. Earlier studies have shown that removal of corticosterone by adrenalectomy, particularly in the dentate gyrus, results in enhanced expression of the 5-HT1A receptor mRNA and increased 5-HT1A receptor binding capacity. This was normalized by activation of mineralocorticoid receptors or concurrent activation of both receptor types. In the present, intracellular recording study in vitro, we examined if the altered levels of 5-HT1A receptor mRNA and protein are associated with changes in the response to 5-HT. We found that the hyperpolarization and resistance decrease induced in granule cells by a submaximal (10 microM) dose of 5-HT were unaltered 2-4 days after adrenalectomy, indicating a dissociation between corticosteroid actions on 5-HT1A receptor mRNA/protein levels and functional responses to 5-HT. Subsequent occupation of mineralocorticoid receptors in vitro significantly suppressed the 5-HT induced change in resistance, 1-4 h after steroid application. Compared to this, concurrent activation of glucocorticoid receptors led to large responses to 5-HT. This modulation by steroids was not observed with a higher dose of 5-HT (30 microM). The data suggest that with moderate amounts of 5-HT, corticosteroids affect the information flow through the dentate gyrus such that excitatory transmission is promoted with predominant mineralocorticoid receptor activation and attenuated with additional glucocorticoid receptor occupation.
大鼠齿状回中的颗粒细胞含有盐皮质激素和糖皮质激素受体，肾上腺激素皮质酮以不同的亲和力与这些受体结合。这些细胞还表达5-羟色胺（5-HT）的各种受体亚型，包括介导膜超极化并伴有膜电阻降低的5-HT1A受体。早期研究表明，通过肾上腺切除术去除皮质酮，特别是在齿状回中，会导致5-HT1A受体mRNA的表达增强和5-HT1A受体结合能力增加。通过激活盐皮质激素受体或同时激活两种受体类型可使这种情况恢复正常。在目前的体外细胞内记录研究中，我们检查了5-HT1A受体mRNA和蛋白质水平的改变是否与对5-HT的反应变化有关。我们发现，肾上腺切除术后2-4天，次最大剂量（10 microM）的5-HT在颗粒细胞中诱导的超极化和电阻降低没有改变，这表明皮质类固醇对5-HT1A受体mRNA/蛋白质水平的作用与对5-HT的功能反应之间存在解离。在体外随后占据盐皮质激素受体可在应用类固醇后1-4小时显著抑制5-HT诱导的电阻变化。与此相比，同时激活糖皮质激素受体导致对5-HT的反应较大。在较高剂量的5-HT（30 microM）下未观察到类固醇的这种调节作用。数据表明，在中等量的5-HT作用下，皮质类固醇会影响通过齿状回的信息流，使得在主要激活盐皮质激素受体时促进兴奋性传递，而在额外占据糖皮质激素受体时则减弱兴奋性传递。
