title: Inhibition of T-type Ca(2+) currents in mouse spermatogenic cells by gossypol, an antifertility compound.
abstract: 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 Ca(2+) and Cl(-) currents in mouse spermatogenic cells obtained by mechanical dissociation. The results showed that gossypol concentration-dependently and irreversibly inhibited T-type Ca(2+) currents in the cells. When the concentration of gossypol was > or =5 microM, the currents were blocked completely. The time to current block was progressively shortened as the gossypol concentration was increased from 5 to 80 microM. 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 Ca(2+) 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 Ca(2+) currents could be responsible for the antifertility activity of the compound, indicating a possibility to use gossypol as a local contraceptive drug.
authors.affiliation: Key Laboratory of Neurobiology, Institute of Physiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, PR China.
authors.forename: Junping
authors.initials: J
authors.lastname: Bai
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000818:Animals; D000988:Antispermatogenic Agents / Q000494:pharmacology; D020747:Calcium Channels, T-Type / Q000502:physiology*; D018118:Chloride Channels / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000378:metabolism; D006072:Gossypol / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D013737:Testis / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors
chemical_list: D000988:Antispermatogenic Agents; D020747:Calcium Channels, T-Type; D018118:Chloride Channels; D011505:Protein-Tyrosine Kinases; D019204:GTP-Binding Proteins; D006072:Gossypol