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Vladimir Matchkov

NS11021, a novel opener of large-conductance Ca(2+)-activated K(+) channels, enhances erectile responses in rats

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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NS11021, a novel opener of large-conductance Ca(2+)-activated K(+) channels, enhances erectile responses in rats. / Kun, Attila; Matchkov, Vladimir; Stankevicius, Edgaras et al.

In: British Journal of Pharmacology, Vol. 158, No. 6, 2009, p. 1465-76.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Harvard

Kun, A, Matchkov, V, Stankevicius, E, Nardi, A, Hughes, A, Kirkeby, HJ, Demnitz, J & Simonsen, U 2009, 'NS11021, a novel opener of large-conductance Ca(2+)-activated K(+) channels, enhances erectile responses in rats', British Journal of Pharmacology, vol. 158, no. 6, pp. 1465-76. https://doi.org/10.1111/j.1476-5381.2009.00404.x

APA

Kun, A., Matchkov, V., Stankevicius, E., Nardi, A., Hughes, A., Kirkeby, H. J., Demnitz, J., & Simonsen, U. (2009). NS11021, a novel opener of large-conductance Ca(2+)-activated K(+) channels, enhances erectile responses in rats. British Journal of Pharmacology, 158(6), 1465-76. https://doi.org/10.1111/j.1476-5381.2009.00404.x

CBE

Kun A, Matchkov V, Stankevicius E, Nardi A, Hughes A, Kirkeby HJ, Demnitz J, Simonsen U. 2009. NS11021, a novel opener of large-conductance Ca(2+)-activated K(+) channels, enhances erectile responses in rats. British Journal of Pharmacology. 158(6):1465-76. https://doi.org/10.1111/j.1476-5381.2009.00404.x

MLA

Kun, Attila et al. "NS11021, a novel opener of large-conductance Ca(2+)-activated K(+) channels, enhances erectile responses in rats". British Journal of Pharmacology. 2009, 158(6). 1465-76. https://doi.org/10.1111/j.1476-5381.2009.00404.x

Vancouver

Kun A, Matchkov V, Stankevicius E, Nardi A, Hughes A, Kirkeby HJ et al. NS11021, a novel opener of large-conductance Ca(2+)-activated K(+) channels, enhances erectile responses in rats. British Journal of Pharmacology. 2009;158(6):1465-76. doi: 10.1111/j.1476-5381.2009.00404.x

Author

Kun, Attila ; Matchkov, Vladimir ; Stankevicius, Edgaras et al. / NS11021, a novel opener of large-conductance Ca(2+)-activated K(+) channels, enhances erectile responses in rats. In: British Journal of Pharmacology. 2009 ; Vol. 158, No. 6. pp. 1465-76.

Bibtex

@article{fd196ff0119b11dfb95d000ea68e967b,
title = "NS11021, a novel opener of large-conductance Ca(2+)-activated K(+) channels, enhances erectile responses in rats",
abstract = "BACKGROUND AND PURPOSE: Large-conductance Ca(2+)-activated K(+) channels (BK(Ca)), located on the arterial and corporal smooth muscle, are potential targets for treatment of erectile dysfunction (ED). This study investigated whether NS11021 (1-(3,5-Bis-trifluoromethyl-phenyl)-3-[4-bromo-2-(1H-tetrazol-5-yl)-phenyl]-thiourea), a novel opener of BK(Ca) channels, relaxes erectile tissue in vitro and enhances erectile responses in intact rats. The effects were compared with sildenafil, an inhibitor of phosphodiesterase type 5. EXPERIMENTAL APPROACH: Patch clamp was used to record whole cell current in rat isolated corpus cavernosum smooth muscle cells (SMCs) and human umbilical vein endothelial cells (HUVECs). Isometric tension was measured in intracavernous arterial rings and corpus cavernosum strips isolated from rats and men, and simultaneous measurements of intracellular Ca(2+) concentration ([Ca(2+)](i)) and tension were performed in intracavernous arteries. Erectile response was measured in anaesthetized rats. KEY RESULTS: In patch clamp recordings, NS11021 increased currents sensitive to the selective BK(Ca) channel blocker, iberiotoxin (IbTX) in SMCs, but did not modulate K(+) current in HUVECs. NS11021 reduced [Ca(2+)](i) and tension in penile arteries. IbTX inhibited the vasorelaxation induced by NS11021 and sildenafil in human erectile tissue. NS11021 and sildenafil but not vehicle increased erectile responses in anaesthetized rats, an effect which was abolished after pretreatment with tetraethylammonium. CONCLUSIONS AND IMPLICATIONS: NS11021 leads to relaxation of both intracavernous arteries and corpus cavernosum strips primarily through opening of BK(Ca) channels. It is also effective in facilitating erectile responses in anaesthetized rats. These results suggest a potential for use of BK(Ca) openers in the treatment of ED.",
author = "Attila Kun and Vladimir Matchkov and Edgaras Stankevicius and Antonio Nardi and Alun Hughes and Kirkeby, {Hans J{\o}rgen} and Joachim Demnitz and Ulf Simonsen",
year = "2009",
doi = "10.1111/j.1476-5381.2009.00404.x",
language = "English",
volume = "158",
pages = "1465--76",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "John/Wiley & Sons Ltd.",
number = "6",

}

RIS

TY - JOUR

T1 - NS11021, a novel opener of large-conductance Ca(2+)-activated K(+) channels, enhances erectile responses in rats

AU - Kun, Attila

AU - Matchkov, Vladimir

AU - Stankevicius, Edgaras

AU - Nardi, Antonio

AU - Hughes, Alun

AU - Kirkeby, Hans Jørgen

AU - Demnitz, Joachim

AU - Simonsen, Ulf

PY - 2009

Y1 - 2009

N2 - BACKGROUND AND PURPOSE: Large-conductance Ca(2+)-activated K(+) channels (BK(Ca)), located on the arterial and corporal smooth muscle, are potential targets for treatment of erectile dysfunction (ED). This study investigated whether NS11021 (1-(3,5-Bis-trifluoromethyl-phenyl)-3-[4-bromo-2-(1H-tetrazol-5-yl)-phenyl]-thiourea), a novel opener of BK(Ca) channels, relaxes erectile tissue in vitro and enhances erectile responses in intact rats. The effects were compared with sildenafil, an inhibitor of phosphodiesterase type 5. EXPERIMENTAL APPROACH: Patch clamp was used to record whole cell current in rat isolated corpus cavernosum smooth muscle cells (SMCs) and human umbilical vein endothelial cells (HUVECs). Isometric tension was measured in intracavernous arterial rings and corpus cavernosum strips isolated from rats and men, and simultaneous measurements of intracellular Ca(2+) concentration ([Ca(2+)](i)) and tension were performed in intracavernous arteries. Erectile response was measured in anaesthetized rats. KEY RESULTS: In patch clamp recordings, NS11021 increased currents sensitive to the selective BK(Ca) channel blocker, iberiotoxin (IbTX) in SMCs, but did not modulate K(+) current in HUVECs. NS11021 reduced [Ca(2+)](i) and tension in penile arteries. IbTX inhibited the vasorelaxation induced by NS11021 and sildenafil in human erectile tissue. NS11021 and sildenafil but not vehicle increased erectile responses in anaesthetized rats, an effect which was abolished after pretreatment with tetraethylammonium. CONCLUSIONS AND IMPLICATIONS: NS11021 leads to relaxation of both intracavernous arteries and corpus cavernosum strips primarily through opening of BK(Ca) channels. It is also effective in facilitating erectile responses in anaesthetized rats. These results suggest a potential for use of BK(Ca) openers in the treatment of ED.

AB - BACKGROUND AND PURPOSE: Large-conductance Ca(2+)-activated K(+) channels (BK(Ca)), located on the arterial and corporal smooth muscle, are potential targets for treatment of erectile dysfunction (ED). This study investigated whether NS11021 (1-(3,5-Bis-trifluoromethyl-phenyl)-3-[4-bromo-2-(1H-tetrazol-5-yl)-phenyl]-thiourea), a novel opener of BK(Ca) channels, relaxes erectile tissue in vitro and enhances erectile responses in intact rats. The effects were compared with sildenafil, an inhibitor of phosphodiesterase type 5. EXPERIMENTAL APPROACH: Patch clamp was used to record whole cell current in rat isolated corpus cavernosum smooth muscle cells (SMCs) and human umbilical vein endothelial cells (HUVECs). Isometric tension was measured in intracavernous arterial rings and corpus cavernosum strips isolated from rats and men, and simultaneous measurements of intracellular Ca(2+) concentration ([Ca(2+)](i)) and tension were performed in intracavernous arteries. Erectile response was measured in anaesthetized rats. KEY RESULTS: In patch clamp recordings, NS11021 increased currents sensitive to the selective BK(Ca) channel blocker, iberiotoxin (IbTX) in SMCs, but did not modulate K(+) current in HUVECs. NS11021 reduced [Ca(2+)](i) and tension in penile arteries. IbTX inhibited the vasorelaxation induced by NS11021 and sildenafil in human erectile tissue. NS11021 and sildenafil but not vehicle increased erectile responses in anaesthetized rats, an effect which was abolished after pretreatment with tetraethylammonium. CONCLUSIONS AND IMPLICATIONS: NS11021 leads to relaxation of both intracavernous arteries and corpus cavernosum strips primarily through opening of BK(Ca) channels. It is also effective in facilitating erectile responses in anaesthetized rats. These results suggest a potential for use of BK(Ca) openers in the treatment of ED.

U2 - 10.1111/j.1476-5381.2009.00404.x

DO - 10.1111/j.1476-5381.2009.00404.x

M3 - Journal article

C2 - 19845682

VL - 158

SP - 1465

EP - 1476

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 6

ER -