虽然据报道内分泌干扰物双酚A(BPA)抑制神经传导,潜在机制尚不清楚.因此,在本研究中,我们使用气隙法检查了BPA对从青蛙坐骨神经记录的复合动作电位(CAPs)的影响。用BPA(0.5mM)治疗坐骨神经20分钟,使CAP的峰值幅度以部分可逆的方式降低了约60%。CAP峰值振幅的降低是浓度依赖性的,半最大抑制浓度(IC50)值为0.31mM。BPA的这种作用不受雌激素受体拮抗剂的影响,4-羟基他莫昔芬,这本身降低了CAP峰值振幅,IC50值为0.26mM(与BPA相当)。天然雌激素17β-雌二醇,在最高可溶解浓度(0.05mM)下,具有类似于BPA的效果。在抑制青蛙CAPs方面,BPA的IC50值与某些局部麻醉药的IC50值相当。我们的发现表明,BPA以独立于雌激素受体的方式抑制神经传导。BPA的这一行为可能是基础,至少在某种程度上,该化合物的神经毒性。
Although the endocrine disruptor bisphenol A (BPA) is reported to inhibit nerve conduction, the underlying mechanisms are unclear. Therefore, in the present study, we examined the effect of BPA on compound action potentials (CAPs) recorded from the frog sciatic nerve using the air-gap method. Treatment of the sciatic nerve with BPA (0.5 mM) for 20 min reduced the peak amplitude of the CAP by approximately 60% in a partially reversible manner. The reduction in the CAP peak amplitude was concentration-dependent, with a half-maximal inhibitory concentration (IC50) value of 0.31 mM. This effect of BPA was unaffected by an estrogen-receptor antagonist, 4-hydroxytamoxifen, which by itself reduced CAP peak amplitude, with an IC50 value of 0.26 mM (comparable to that of BPA). The natural estrogen 17β-estradiol, at the highest dissolvable concentration (0.05 mM), had an effect similar to that of BPA. The IC50 value of BPA was comparable to those of some local anesthetics in inhibiting frog CAPs. Our findings suggest that BPA inhibits nerve conduction in a manner independent of estrogen receptors. This action of BPA may underlie, at least in part, the neurotoxicity of the compound.