Shimizu M, Nishida A, Zensho H, Miyata M, Yamawaki S
Department of Psychiatry and Neuroscience, Institute of Clinical Research, Kure National Hospital, Japan.
J Neurochem. 1997 Jun;68(6):2604-9. doi: 10.1046/j.1471-4159.1997.68062604.x.
Astrocytes derived from rat frontal cortex contain 5-hydroxytryptamine7 (5-HT)7 receptors positively coupled to adenylyl cyclase. In the present study, we investigated the effects of glucocorticoids on adenylyl cyclase activity and 5-HT7 receptor gene expression in astrocytes. Addition of dexamethasone (0.01-100 nM, 12-72 h) to the culture medium decreased cyclic AMP formation induced by 5-HT in a time- and concentration-dependent manner. Dexamethasone treatment (10 nM, 48 h) reduced maximum responses of cyclic AMP formation induced by 5-HT and 5-carboxamidotryptamine without alterations in the EC50 value. In contrast, treatment with the mineralocorticoid aldosterone (48 h) had no significant effects on 5-HT-induced cyclic AMP formation with concentrations up to 10 nM. It was observed that dexamethasone treatment (1-100 nM, 3-72 h) also decreased the expression of 5-HT7 receptor mRNA, using reverse transcription and polymerase chain reaction analysis. A significant reduction in expression of 5-HT7 mRNA appeared at 3 h of dexamethasone treatment and reached a maximum at 6 h of treatment. On the other hand, dexamethasone treatment (10 nM, 48 h) did not affect basal levels of cyclic AMP and cyclic AMP synthesis stimulated by isoproterenol, N-ethylcarboxamidoadenosine, cholera toxin, and forskolin. These results suggest that dexamethasone decreases the expression of the 5-HT7 receptor gene and, consequently, 5-HT7 receptor-mediated signal transduction in frontocortical astrocytes.
源自大鼠额叶皮质的星形胶质细胞含有与腺苷酸环化酶正向偶联的5-羟色胺7（5-HT）7受体。在本研究中，我们研究了糖皮质激素对星形胶质细胞中腺苷酸环化酶活性和5-HT7受体基因表达的影响。向培养基中添加地塞米松（0.01 - 100 nM，12 - 72小时）以时间和浓度依赖性方式降低了5-HT诱导的环磷酸腺苷（cAMP）形成。地塞米松处理（10 nM，48小时）降低了5-HT和5-羧酰胺色胺诱导的cAMP形成的最大反应，而EC50值没有改变。相比之下，用盐皮质激素醛固酮处理（48小时）对浓度高达10 nM的5-HT诱导的cAMP形成没有显著影响。通过逆转录和聚合酶链反应分析观察到，地塞米松处理（1 - 100 nM，3 - 72小时）也降低了5-HT7受体mRNA的表达。地塞米松处理3小时时，5-HT7 mRNA表达显著降低，处理6小时时达到最大值。另一方面，地塞米松处理（10 nM，48小时）不影响异丙肾上腺素、N-乙基羧酰胺腺苷、霍乱毒素和福斯高林刺激的cAMP基础水平和cAMP合成。这些结果表明，地塞米松降低了5-HT7受体基因的表达，从而降低了额叶皮质星形胶质细胞中5-HT7受体介导的信号转导。
