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  • Title: Effects of raloxifene on voltage-dependent T-type Ca2+ channels in mouse spermatogenic cells.
    Author: Wang Q, Lu L, Gao X, Wang C, Wang J, Cheng J, Gao R, Xiao H.
    Journal: Pharmacology; 2011; 87(1-2):70-80. PubMed ID: 21228613.
    Abstract:
    Voltage-dependent T-type Ca(2+) channels have eminent roles in sperm function. In the present study, we investigated the effects of raloxifene, a selective estrogen receptor modulator, on T-type Ca(2+) channels in mouse spermatogenic cells by using both electrophysiological and molecular techniques. We found that T-type calcium currents (I(T-Ca)) were inhibited by raloxifene in a concentration-dependent manner with an IC(50) of 2.97 μM, as assessed with the patch clamp technique. Application of raloxifene at 2 μM inhibited I(T-Ca) by 54.9 ± 2.1% at -20 mV (n = 10, p < 0.05). Furthermore, raloxifene-induced inhibition of I(T-Ca) was associated with a negative shift of both the activation and the steady-state inactivation properties. The time constants of activation and inactivation were decreased, the time constant of deactivation was increased, but the time constant of recovery was not affected. In addition, the inhibitory effects of raloxifene and 17β-estradiol on I(T-Ca) were unaffected by the estrogen receptor antagonist ICI 182,780. We also found that raloxifene treatment decreased the mRNA expression of Ca(V)3.2 and Ca(V)3.3, but not Ca(V)3.1 in GC-2spd (ts) cells (mouse spermatocyte cell line), as assessed by real-time RT-PCR. Taken together, these data indicate that in mouse spermatogenic cells, raloxifene decreases I(T-Ca) independent of classical estrogen, and the mRNA expression of T-type calcium channels and therefore may affect male reproductive function.
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