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Abstract

Tamoxifen (estrogen antagonist) inhibits voltage-gated calcium current and contractility in vascular smooth muscle from rats.

J Song, P R Standley, F Zhang, D Joshi, S Gappy, J R Sowers and J L Ram
Journal of Pharmacology and Experimental Therapeutics June 1996, 277 (3) 1444-1453;
J Song
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P R Standley
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F Zhang
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D Joshi
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S Gappy
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J R Sowers
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J L Ram
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Abstract

Tamoxifen (Tx) has been used in breast cancer treatment and prophylaxis because of its antiestrogenic activity; however, Tx may also have beneficial cardiovascular effects and other actions mediated by mechanisms other than estrogen receptors. Previous studies showing interactions of Tx with Ca+(+)-channel blockers suggested that Tx may affect Ca++ channels, an hypothesis that was investigated using whole cell patch clamp techniques in vascular smooth muscle cells (cell line A7r5 and freshly dissociated cells) and by determining effects on contractions of isolated blood vessels. Tx reduced current through L-type Ca+2 channels, with an ID50 of 2 x 10(-6) M when applied by cumulative addition to A7r5 cells. With acute application, 10(-6) M Tx significantly reduced L-type current in A7r5 cells within 2 min to 88% of control (vehicle, 0.1% ethanol) in A7r5 cells, 67% of control in aortic vascular smooth muscle cells, and 60% of control in tail artery vascular smooth muscle cells. Tx also decreased the rate of inactivation of L-type current. Inhibition of T-type current by Tx was less than for L-type current but was significant at 10(-5) M Tx. Treatment of tail artery rings with Tx (10(-5) M, 15 min; 10(-6) M, 4 hr) reduced K+-elicited contractions. Since therapeutic concentrations of Tx during treatment may exceed 10(-6) M, these effects of Tx on vascular smooth muscle Ca++ channels and vessel contractions may have a role in the efficacy and side-effects of Tx treatment.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 277, Issue 3
1 Jun 1996
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Abstract

Tamoxifen (estrogen antagonist) inhibits voltage-gated calcium current and contractility in vascular smooth muscle from rats.

J Song, P R Standley, F Zhang, D Joshi, S Gappy, J R Sowers and J L Ram
Journal of Pharmacology and Experimental Therapeutics June 1, 1996, 277 (3) 1444-1453;

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Abstract

Tamoxifen (estrogen antagonist) inhibits voltage-gated calcium current and contractility in vascular smooth muscle from rats.

J Song, P R Standley, F Zhang, D Joshi, S Gappy, J R Sowers and J L Ram
Journal of Pharmacology and Experimental Therapeutics June 1, 1996, 277 (3) 1444-1453;
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