Archive for the 'Progesterone' Category

09 May

Progesterone-Mediated Calcium Influx: 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 […]

08 May

Progesterone-Mediated Calcium Influx: DISCUSSION(5)

Mibefradil demonstrates a use-dependent inhibition (IC50 = 5 ^M) of T-type currents in mouse spermatogenic cells; and in somatic cells, mibefradil selectively inhibits T-type channels over high voltage-activated (e.g., L-type) Ca2+ channels (e.g., IC50 1.6 ^M and 28 ^M, respectively) in a voltage-dependent and use-dependent manner. In human spermatozoa, however, there was no difference in […]

07 May

Progesterone-Mediated Calcium Influx: DISCUSSION(4)

It has been proposed that the inhibitory actions of pimozide on the zona pellucida-initiated [Ca2+]i elevation reflect the preferential blockade of T-type currents in mouse sperm, because spermatogenic cells demonstrate T-type currents that are inhibited by pimozide at similar concentrations (IC50 = 0.5 ^M) and because they lack L-type currents. However, in other cell types, […]

06 May

Progesterone-Mediated Calcium Influx: DISCUSSION(3)

Is a VOCCT Involved in the P4-Activated Ca2+ Influx? T-type Ca2+ currents in mouse spermatogenic cells have a low voltage activation threshold, exhibit rapid inactivation, and demonstrate steady-state inactivation in the -90 to -40 mV range. Therefore, at the resting membrane potential of uncapacitated mouse spermatozoa (~—40 mV), a large fraction of the T-type channels […]

05 May

Progesterone-Mediated Calcium Influx: DISCUSSION(2)

Unlike sper-matogenic cells, spermatozoa are not amenable to electro-physiological experiments, thus precluding characterization of the Ca2+ influx pathway on the basis of its biophysical properties. An added complication of trying to identify the involvement of VOCC in the P4-activated Ca2+ influx is the absence of pharmacological tools with sufficient selectivity and potency. Recently, however, a […]

04 May

Progesterone-Mediated Calcium Influx: DISCUSSION(1)

P4 stimulates Ca2+ influx in both uncapacitated and capacitated spermatozoa. Previous comparisons between these two populations in the same experiment were contradictory and suggested that the amplitude of the P4-activated Ca2+ influx was similar or greater in the capacitated population. Our results are in agreement with those of the latter studies and indicate that both […]

03 May

Progesterone-Mediated Calcium Influx: RESULTS(5)

Pharmacological Characterization of the P4-Initiated AR Capacitated spermatozoa from a total of seven different donors were used to examine the effects of pimozide, mi-befradil, and calmidazolium on the P4-initiated AR. Since pimozide or calmidazolium alone produced an elevation of the [Ca2+]i, we investigated whether these drugs could initiate the AR. The percentages of acrosome-reacted spermatozoa […]

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