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  • Title: Progesterone-mediated calcium influx and acrosome reaction of human spermatozoa: pharmacological investigation of T-type calcium channels.
    Author: Garcia MA, Meizel S.
    Journal: Biol Reprod; 1999 Jan; 60(1):102-9. PubMed ID: 9858492.
    Abstract:
    The mechanisms of the progesterone (P4)-activated Ca2+ influx and the relationship between the intracellular free Ca2+ concentration ([Ca2+]i) and the acrosome reaction (AR) were investigated in this study. We compared the [Ca2+]i of uncapacitated and capacitated human sperm populations in response to P4 stimulation; characterized the effects of the pharmacological agents pimozide and mibefradil, inhibitors of T-type voltage-operated calcium channels (VOCCT), on the P4-activated Ca2+ influx; and determined the effects of these drugs on the P4-initiated AR. Since pimozide can also inhibit calmodulin-dependent enzymes, we examined the effects of the calmodulin antagonist, calmidazolium, on the above-mentioned events. The basal [Ca2+]i and the amplitude of the P4-activated Ca2+ influx were significantly (p < 0.05) higher in capacitated sperm populations. Also, in capacitated sperm populations, all three pharmacological agents significantly (p < 0.05) inhibited the P4-activated Ca2+ influx (IC50): calmidazolium (0.7 microM) > pimozide (8 microM) > mibefradil (11 microM). By contrast, the effects of these drugs on the P4-initiated AR were varied: pimozide (10 and 20 microM) significantly (p < 0.05) increased the percentage of AR spermatozoa, calmidazolium was without effect, and mibefradil (20 microM) significantly (p < 0.05) inhibited the AR. These disparate results do not allow us to reach any definitive conclusion concerning the role of a sperm VOCCT in the mechanism of the P4-initiated AR. However, the differences between the [Ca2+]i and AR effects, in particular the inverse relationship in the case of pimozide, suggest a dissociation between the amplitude of the P4-stimulated Ca2+ signal and the downstream biological effect of that signal, the AR.
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