09 May

Progesterone-Mediated Calcium Influx: DISCUSSION(6)

DISCUSSION(6)

Here we report that pimozide, mibefradil, and calmidazolium— drugs that inhibit the P4-activated Ca2+ influx to the same magnitude—poOentiate,inhibit,andhavenoeffectonthe P4-initiated AR, respectively. The inhibition of the P4-ini-tiated AR by mibefradil may suggest the involvement of a VVCCT; however, the concentration of mibefradil (20 ^M) required to inhibit the P4-initiated AR is higher than that needed to inhibit Ca2+ influx in spermatozoa (IC50 = 11 ^M) and spermatogenic cells (5 ^M). Furthermore, this concentration of mibefradil is sufficiently high that it does not facilitate distinction between T-type and L-type channels. Therefore, the disparate results obtained with the T-channel blockers, mibefradil and pimozide, and the high levels of mibefradil required to inhibit the AR do not allow us to conclude whether or not a VVCCT is involved in the P4-initiated AR. ampicillin antibiotic

Pimozide at a 1-^M concentration inhibits the zona pel-lucida-induced Ca2+ influx and AR of mouse spermatozoa. In contrast, our result indicated that pimozide at a 10fold higher concentration inhibited the P4-activated Ca2+ influx (Fig. 4) but potentiated the P4-initiated AR (Fig. 7). The mechanism of this stimulatory activity is unknown and apparently not mediated by a calmodulin-dependent pathway, given the lack of any significant (p = 0.98, n = 5) effect by calmidazolium (0.1-2 ^M) on the P4-initiated AR. More importantly, though, the inverse relationship between the actions of pimozide on the P4-activated Ca2+ influx and the P4-initiated AR (Fig. 7) suggests that the ability of P4 to produce a biological effect (i.e., AR) is not dependent on the amplitude of the [Ca2+]i elevation produced by this steroid hormone.

Categories: Progesterone
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