Pregnenolone sulphate-independent inhibition of TRPM3 channels by progesterone.
Bottom Line: Progesterone metabolites and 17β-oestradiol were also inhibitory but the effects were relatively small.Corticosteroids lacked effect.Relevance of TRPM3 or the progesterone effect to ovarian cells, which have been suggested to express TRPM3, was not identified.
Affiliation: Multidisciplinary Cardiovascular Research Centre, University of Leeds, Leeds, UK.Show MeSH
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Mentions: A mechanism by which progesterone might act on TRPM3 is via a classical progesterone receptor. To investigate this possibility, cells were pre-incubated with the progesterone receptor antagonist mifepristone . At 1–2 μM mifepristone strongly antagonises the progesterone receptor. Mifepristone (2 μM) had an effect of its own on TRPM3-mediated Ca2+ influx (24% inhibition) but sufficient TRPM3 activity remained to test progesterone (Fig. 7a, b). The inhibition caused by progesterone in the presence of mifepristone was slightly more than in the absence of mifepristone (52% cf. 44% inhibition) (Fig. 7a, b). Mifepristone (1 μM) had no effect of its own on TRPM3 and also did not inhibit the effect of progesterone (data not shown). The data suggest that progesterone did not act on TRPM3 through classical progesterone receptors.
Affiliation: Multidisciplinary Cardiovascular Research Centre, University of Leeds, Leeds, UK.