Butyl benzyl phthalate (BBP), a plasticizer and an environmental pollutant, exerts genomic estrogenic-like effects via estrogen receptors. In addition to exerting genomic effects via intracellular steroid receptors, estrogen exerts non-genomic effects through interactions with membrane ion channels to lead the rapid alteration of neuronal excitability. Estradiol is known as to have modulating role on nicotinic acetylcholine receptors (nAChR). We investigated the possibility of BBP exerting non-genomic estrogenic-like effects on nAChR in bovine adrenal chromaffin cells. Our results show that BBP inhibited Ca2+ signaling induced by the nicotinic ligands carbachol, 1,1-dimethyl-4-phenyl-piperazinium iodide (DMPP) and epibatidine (IC50 levels of 4.3, 4.1, 5.4 microM, respectively) as well as high K+ solution (IC50 50.9 microM). Additionally, in the electrophysiological observations, BBP blocked the inward current coupled with nAChR under the stimulation of carbachol. We, therefore, suggest that nAChR and voltage-gated Ca2+ channels are major and minor sites, respectively, of BBP action on the plasma membrane. The inhibitory effect of BBP on nAChR was found to be both noncompetitive and reversible, remaining unchanged as nAChR ligand concentration increased and decreased after washing. BBP was 10 times more potent than estradiol in inhibiting nAChR-coupled Ca2+ signals. We conclude that BBP exerts a novel rapidly inhibitory effect on nAChR.

中文翻译：

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邻苯二甲酸丁苄酯可阻断牛肾上腺嗜铬细胞中的Ca2 +信号传导和儿茶酚胺分泌以及烟碱乙酰胆碱受体。

邻苯二甲酸丁苄酯（BBP）是一种增塑剂和环境污染物，它通过雌激素受体发挥类似基因组的雌激素作用。除了通过细胞内类固醇受体发挥基因组作用外，雌激素还通过与膜离子通道的相互作用来发挥非基因组作用，从而导致神经元兴奋性的快速改变。雌二醇已知对烟碱乙酰胆碱受体（nAChR）具有调节作用。我们调查了BBP对牛肾上腺嗜铬细胞中nAChR发挥非基因组雌激素样作用的可能性。我们的结果表明，BBP抑制了烟碱配体卡巴胆碱，1,1-二甲基-4-苯基碘化哌嗪酮（DMPP）和依巴替丁诱导的Ca2 +信号传导（IC50分别为4.3、4.1、5.4 microM）和高K +溶液（IC50 50.9 microM）。另外，在电生理观察中，BBP在卡巴胆碱的刺激下阻断了与nAChR耦合的内向电流。因此，我们建议nAChR和电压门控的Ca2 +通道分别是BBP作用在质膜上的主要和次要部位。发现BBP对nAChR的抑制作用是非竞争性的和可逆的，随着nAChR配体浓度在洗涤后增加和减少而保持不变。在抑制nAChR偶联的Ca2 +信号方面，BBP的效力比雌二醇高10倍。我们得出的结论是BBP对nAChR发挥了新型的快速抑制作用。BBP对质膜的作用 发现BBP对nAChR的抑制作用是非竞争性的和可逆的，随着nAChR配体浓度在洗涤后增加和减少而保持不变。在抑制nAChR偶联的Ca2 +信号方面，BBP的效力比雌二醇高10倍。我们得出的结论是BBP对nAChR发挥了新型的快速抑制作用。BBP对质膜的作用 发现BBP对nAChR的抑制作用是非竞争性的和可逆的，随着nAChR配体浓度在洗涤后增加和减少而保持不变。在抑制nAChR偶联的Ca2 +信号方面，BBP的效力比雌二醇高10倍。我们得出的结论是BBP对nAChR发挥了新型的快速抑制作用。