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Modulation of sympathetic nervous system by environmental estrogens : Molecular and pharmacological analysis in adrenal medulla

环境雌激素对交感神经系统的调节：肾上腺髓质的分子和药理学分析

基本信息

批准号：
11839030
负责人：
TOYOHIRA Yumiko
金额：
$ 2.3万
依托单位：
University of Occupational and Environmental Health
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

Environmental estrogens are nonsteroidal manmade chemicals that can enter the body by ingestion or absorption and mimic the action of estrogens. Environmental estrogens have been reported to modulate sexual differentiation by interacting with nuclear steroid receptors. The focus has been on reproductive organs, but sex steroids have far more widespread actions. Estrogen has been reported to modulate the function of neurotransmitter receptors, transporters and ionic channels via nongenomic mechanisms. In the present study, to investigate the influence of environmental estrogens on neuro-endocrine system, we examined the effects of bisphenol A and nonylphenol on catecholamine secretion and uptake in cultured bovine adrenal medullary cells.Bisphenol A significantly inhibited the uptake of [^3H] noradrenaline by the cells in a concentration-dependent manner (1-100 μM). The effect was associated with a decrease in the maximal velocity of the transport process with no significant change in t … More he Michaelis-Menten constant. Treatment of the cells with 17β-estradiol reproduced the inhibitory effects of bisphenol A on the norepinephrine transporter activity. Scatchard analysis of [^3H] desipramine binding revealed that bisphenol A decreased the maximal binding and increased the dissociation constant. Bisphenol A inhibited carbachol-induced catecholamine secretion, ^<45>Ca and ^<22>Na influx in a concentration-dependent manner (10-100 μM). It also inhibited veratridine and high K-induced responses in a concentration-dependent manner. Treatment of the cells with nonylphenol led to a significant inhibition of carbachol-induced catecholamine secretion and ^<45>Ca influx via an activation of nicotinic acetylcholine receptor in a concentration (10-100 μM) - and time (2-72 h) - dependent manner. It also inhibited veratridine-induced responses via an activation of voltage-dependent Na channels, whereas it had little effect on catecholamine secretion caused by high K, a direct activation of voltage-dependent Ca channels.These results suggest that environmental estrogens modulate the sympathetic nervous activity through inhibition of receptor, ion channel and transporter in non-genomic manner. Less

环境雌激素是非甾体类人造化学品，可以通过摄入或吸收进入人体，并模仿雌激素的作用。据报道，环境雌激素通过与核类固醇受体相互作用来调节性分化。重点一直是生殖器官，但性类固醇有更广泛的行动。雌激素通过非基因组机制调节神经递质受体、转运蛋白和离子通道的功能。为探讨环境雌激素对神经内分泌系统的影响，本研究观察了双酚A和壬基酚对培养的牛肾上腺髓质细胞分泌和摄取儿茶酚胺的影响，双酚A以浓度依赖的方式（1-100 μM）显著抑制细胞摄取[^3H]去甲肾上腺素。这种效应与转运过程的最大速度降低有关，而在转运过程中没有显著变化。 ...更多信息米氏常数。用17β-雌二醇处理细胞再现了双酚A对去甲肾上腺素转运体活性的抑制作用。[^3H]地昔帕明结合的Scatchard分析表明，双酚A降低了最大结合，增加了解离常数。双酚A以浓度依赖性方式（10-100 μM）抑制卡巴胆碱诱导的儿茶酚胺分泌、^<45>Ca和^<22>Na内流。它还以浓度依赖性方式抑制藜芦碱和高K诱导的反应。用壬基酚处理细胞，<45>通过激活烟碱乙酰胆碱受体，以浓度（10-100 μM）和时间（2-72 h）依赖性方式显著抑制卡巴胆碱诱导的儿茶酚胺分泌和^ Ca内流。环境雌激素还通过激活电压依赖性Na通道抑制藜芦碱诱导的反应，而对高钾直接激活电压依赖性Ca通道引起的儿茶酚胺分泌影响不大，提示环境雌激素通过抑制受体、离子通道和转运蛋白等非基因组方式调节交感神经活动。少