Ovarian steroid regulation of 5-HT1A receptor binding and G protein activation in female monkeys
Ovarian steroid regulation of 5-HT1A receptor binding and G protein activation in female monkeys
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DOI：
10.1016/s0893-133x(01)00423-7
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发表时间：
2002-07-01
影响因子：
7.6
通讯作者：
Bethea, CL
中科院分区：
文献类型：
--
作者：
Lu, NZ;Bethea, CL
血清素 5-HT1A 受体在血清素神经传递和心理健康中发挥着重要作用。我们之前证明雌二醇 (E) 和孕酮 (P) 会降低猕猴中 5-HT1A 自身受体 mRNA 水平。在本研究中，我们质疑 E 和 P 是否调节 5-HT1A 结合和功能以及 G(α) 亚基蛋白表达。分别使用 PHIS-OH-DPAT 和 [S-35]GTP-gamma-S 对来自四个治疗组的恒河猴脑切片进行 5-HT1A 受体和 G 蛋白的定量放射自显影：卵巢切除对照组（OVX）、E（28 天）、P（28 天）和 E（28 天）phis P（最后 14 天）治疗组。对经过 OVX 或用马雌激素处理 OVX（EE，30 个月）的食蟹猴中缝提取物进行 G(α) 亚基的蛋白质印迹分析。在下丘脑中，E 或 E + P 但单独的 P 会降低突触后 5-HT1A 结合位点。在中缝背核 (DRN) 中，El P 和 E + P 处理降低了 5-HT1A 自身受体结合。每个治疗组的 8-OH-DPAT 的 Kd 值相同。激素替代期间，基础和 R-(+)-8-OH-DPAT 刺激的 [S-35]GTP-gamma-S 结合均减少，而受体和 G 蛋白之间的偶联效率保持不变。最后，EE 治疗降低了 DRN 中 G(alphai3) 的水平，但没有降低 G(alphai1)、G(alphao) 和 G(alphaz) 的水平。总之，这些观察结果表明，卵巢激素可能部分通过减少 5-HT1A 自身受体、5-HT1A 突触后受体和细胞内信号转导的抑制性 G 蛋白来增加血清素神经传递。 (C) 2002 年美国神经精神药理学学院。由爱思唯尔科学公司出版
Serotonin 5-HT1A receptors play an important role in serotonin neurotransmission and mental health. We previously demonstrated that estradiol (E) and progesterone (P) decrease 5-HT1A autoreceptor mRNA levels in macaques. In this study, we questioned whether E and P regulate 5-HT1A binding and function and G(alpha) subunit protein expression. Quantitative autoradiography for 5-HT1A receptors and G proteins using PHIS-OH-DPAT and [S-35]GTP-gamma-S, respectively, was performed on brain sections of rhesus macaques from four treatment groups: ovariectomized controls (OVX), E (28 d), P (28 d), and E (28 d) phis P (the last 14 d) treated. Western blot analysis for G(alpha) subunits was performed on raphe extracts from cynomolgus macaques that were OVX or OVX treated with equine estrogens (EE, 30 months). In the hypothalamus, E or E + P but not P alone decreased postsynaptic 5-HT1A binding sites. In the dorsal raphe nucleus (DRN), El P, and E + P treatments decreased 5-HT1A autoreceptor binding. The Kd values for 8-OH-DPAT were the same for each treatment group. Both the basal and the R-(+)-8-OH-DPAT stimulated [S-35]GTP-gamma-S binding were decreased during hormone replacement whereas the coupling efficiency between the receptor and G proteins was maintained. Finally, EE treatment reduced the level of G(alphai3), but not G(alphai1), G(alphao), and G(alphaz), in the DRN. In conclusion, these observations suggest that ovarian hormones may increase serotonin neurotransmission, in part, by decreasing 5-HT1A autoreceptors, 5-HT1A postsynaptic receptors, and the inhibitory G proteins for intracellular signal transduction. (C) 2002 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.