Inhibition of T-type Ca(2+) currents in mouse spermatogenic cells by gossypol, an antifertility compound.
Inhibition of T-type Ca(2+) currents in mouse spermatogenic cells by gossypol, an antifertility compound.
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DOI：
10.1016/s0014-2999(02)01315-8
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发表时间：
2002-04
影响因子：
5
通讯作者：
J. Bai;Yuliang Shi
中科院分区：
文献类型：
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作者：
J. Bai;Yuliang Shi
棉酚是从棉花中分离出来的一种雄性不育化合物，已被证明能抑制人类和哺乳动物精子的获能和顶体反应。本文采用全细胞记录技术，观察了棉酚对机械分离的小鼠生精细胞Ca ~（2+）和Cl ~-电流的影响。结果表明，棉酚浓度依赖性地不可逆地抑制细胞T型钙电流。当棉酚浓度≥5 μM时，电流被完全阻断。当棉酚浓度从5 μ M增加到80 μM时，电流阻断时间逐渐缩短。此外，药物以浓度依赖性方式增加失活时间常数，而不影响电流的激活。对T型钙电流的抑制作用与G蛋白介导的信号转导和酪氨酸磷酸化无关。棉酚对Cl-电流无明显影响。这些数据表明，棉酚诱导的抑制T型钙电流可能是负责的化合物的抗生育活性，表明棉酚作为局部避孕药的可能性。
Gossypol, a male antifertility compound isolated from cotton, has been proved to inhibit capacitation and the acrosome reaction in human and mammalian sperm. Here, by using whole-cell recording, we observed the effects of gossypol on Ca2+and Cl−currents in mouse spermatogenic cells obtained by mechanical dissociation. The results showed that gossypol concentration-dependently and irreversibly inhibited T-type Ca2+currents in the cells. When the concentration of gossypol was ≥5 μM, the currents were blocked completely. The time to current block was progressively shortened as the gossypol concentration was increased from 5 to 80 μM. Moreover, the drug increased the time constant of inactivation in a concentration-dependent manner, while it did not affect the activation of the current. The inhibitory effect on the T-type Ca2+current did not correlate with signaling mediated by G proteins and tyrosine phosphorylation. No obvious effect of gossypol on Cl−currents was observed. These data suggest that the gossypol-induced inhibition of T-type Ca2+currents could be responsible for the antifertility activity of the compound, indicating a possibility to use gossypol as a local contraceptive drug.