title: Effects of demethylzeylasteral and celastrol on spermatogenic cell Ca2+ channels and progesterone-induced sperm acrosome reaction.
abstract: The male antifertility effect of a water-chloroform extract of Tripterygium wilfordii Hook. f. (GTW) and several monomers isolated from GTW has attracted worldwide interest. In the present study, the effects of two isolated monomers from GTW, demethylzeylasteral and celastrol, on the Ca(2+) channels in mouse spermatogenic cells and on the sperm acrosome reaction were investigated by whole-cell patch-clamp recording and chlortetracycline staining methods, respectively. The results showed that demethylzeylasteral concentration-dependently and in a partially reversible manner inhibited the Ca(2+) current in spermatogenic cells with an IC(50) of 8.8 microg/ml. Celastrol decreased the Ca(2+) current in the cells time-dependently and irreversibly. The changes in the activation and inactivation time constants of Ca(2+) currents after application of these two compounds were also examined. Demethylzeylasteral increased both activation and inactivation time constants of Ca(2+) currents, and celastrol had no significant effect on them. The two compounds also inhibited significantly the sperm acrosome reaction initiated by progesterone. These data suggest that inhibition of Ca(2+) currents could be responsible for the antifertility activity of these compounds.
authors.affiliation: Key Laboratory of Neurobiology, Institute of Physiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, 200031, Shanghai, PR China.
authors.forename: Jun-Ping
authors.initials: JP
authors.lastname: Bai
authors.forename: Yu-Liang
authors.initials: YL
authors.lastname: Shi
authors.forename: Xin
authors.initials: X
authors.lastname: Fang
authors.forename: Qi-Xian
authors.initials: QX
authors.lastname: Shi
mesh_terms: D020101:Acrosome Reaction / Q000187:drug effects*; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000502:physiology*; D002392:Catechin / Q000494:pharmacology; D003272:Contraceptive Agents, Male / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006072:Gossypol / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D053978:Pentacyclic Triterpenes; D011374:Progesterone / Q000494:pharmacology*; D013094:Spermatozoa / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D015220:Calcium Channels; D003272:Contraceptive Agents, Male; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; C099855:demethylzeylasteral; D011374:Progesterone; D000584:Amiloride; D002392:Catechin; D006072:Gossypol; C050414:celastrol