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Pregnenolone sulphate-independent inhibition of TRPM3 channels by progesterone.

Majeed Y, Tumova S, Green BL, Seymour VA, Woods DM, Agarwal AK, Naylor J, Jiang S, Picton HM, Porter KE, O'Regan DJ, Muraki K, Fishwick CW, Beech DJ - Cell Calcium (2011)

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.

View Article: PubMed Central - PubMed

Affiliation: Multidisciplinary Cardiovascular Research Centre, University of Leeds, Leeds, UK.

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Insensitivity of the progesterone effect to mifepristone. Data were generated by Ca2+ measurement in cells over-expressing TRPM3 (Tet+). (a) Cells were treated with 2 μM mifepristone (mfp) or vehicle for 30 min prior to experiments and mfp was maintained during the recordings. Pre-treatment with 10 μM progesterone (prog) was as described in Fig. 1b, and PregS was applied at 1 μM. (b) Mean data for experiments exemplified in (a), showing the effect of prog alone (+10 prog), mfp alone (+2 mfp), or prog with mfp (+10 prog + 2 mfp) on the PregS-induced response (N/n = 40/5 for each condition).
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fig0035: Insensitivity of the progesterone effect to mifepristone. Data were generated by Ca2+ measurement in cells over-expressing TRPM3 (Tet+). (a) Cells were treated with 2 μM mifepristone (mfp) or vehicle for 30 min prior to experiments and mfp was maintained during the recordings. Pre-treatment with 10 μM progesterone (prog) was as described in Fig. 1b, and PregS was applied at 1 μM. (b) Mean data for experiments exemplified in (a), showing the effect of prog alone (+10 prog), mfp alone (+2 mfp), or prog with mfp (+10 prog + 2 mfp) on the PregS-induced response (N/n = 40/5 for each condition).

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 [17]. 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.


Pregnenolone sulphate-independent inhibition of TRPM3 channels by progesterone.

Majeed Y, Tumova S, Green BL, Seymour VA, Woods DM, Agarwal AK, Naylor J, Jiang S, Picton HM, Porter KE, O'Regan DJ, Muraki K, Fishwick CW, Beech DJ - Cell Calcium (2011)

Insensitivity of the progesterone effect to mifepristone. Data were generated by Ca2+ measurement in cells over-expressing TRPM3 (Tet+). (a) Cells were treated with 2 μM mifepristone (mfp) or vehicle for 30 min prior to experiments and mfp was maintained during the recordings. Pre-treatment with 10 μM progesterone (prog) was as described in Fig. 1b, and PregS was applied at 1 μM. (b) Mean data for experiments exemplified in (a), showing the effect of prog alone (+10 prog), mfp alone (+2 mfp), or prog with mfp (+10 prog + 2 mfp) on the PregS-induced response (N/n = 40/5 for each condition).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3275754&req=5

fig0035: Insensitivity of the progesterone effect to mifepristone. Data were generated by Ca2+ measurement in cells over-expressing TRPM3 (Tet+). (a) Cells were treated with 2 μM mifepristone (mfp) or vehicle for 30 min prior to experiments and mfp was maintained during the recordings. Pre-treatment with 10 μM progesterone (prog) was as described in Fig. 1b, and PregS was applied at 1 μM. (b) Mean data for experiments exemplified in (a), showing the effect of prog alone (+10 prog), mfp alone (+2 mfp), or prog with mfp (+10 prog + 2 mfp) on the PregS-induced response (N/n = 40/5 for each condition).
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 [17]. 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.

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.

View Article: PubMed Central - PubMed

Affiliation: Multidisciplinary Cardiovascular Research Centre, University of Leeds, Leeds, UK.

Show MeSH
Related in: MedlinePlus