钾通道开放剂YM934对猪逼尿肌平滑肌电场刺激收缩反应的影响。

Effect of the potassium channel opener YM934 on the contractile response to electrical field stimulation in pig detrusor smooth muscle.

作者信息

Masuda N, Uchida W, Shirai Y, Shibasaki K, Goto K, Takenaka T

机构信息

Institute of Basic Medical Sciences, Tsukuba University, Japan.

出版信息

J Urol. 1995 Nov;154(5):1914-20.

PMID:7563383

Abstract

PURPOSE

The effect of a potassium channel opener, YM934, on the contractile response to excitatory neurotransmitters was investigated in isolated pig detrusor smooth muscle.

MATERIALS AND METHODS

Electrical field stimulation (EFS; 5 second trains, 50 V, 0.8 msec. duration), alpha, beta-MeATP (3 x 10(-7) to 10(-5) M.) or carbachol (3 x 10(-8) to 10(-6) M.) produced a contractile response in isolated pig detrusor smooth muscle. The effect of YM934 on the contractile responses was evaluated in comparison with the antagonism of the putative cotransmitters, acetylcholine and ATP.

RESULTS

A tetrodotoxin-sensitive, frequency-dependent contractile response to electrical field stimulation was obtained. Atropine (3 x 10(-8) M.) significantly inhibited the contractile response at high frequencies, whereas alpha, beta-MeATP (5 x 10(-6) M.) (desensitizer of P2X-purinoceptors) significantly inhibited the response at low frequencies. YM934 (10(-8) to 10(-7) M.) dose-dependently inhibited the nerve-mediated contractile responses to all frequencies but preferentially at low frequencies, by analogy with alpha, beta-MeATP. A combination of YM934 (3 x 10(-8) M.) and atropine (3 x 10(-8) M.) reduced the response at all frequencies to between 10 and 20% of control, an effect similar to that obtained with alpha, beta-MeATP (5 x 10(-6) M.) and atropine (3 x 10(-8) M.). In addition, YM934 (3 x 10(-8) M.) markedly inhibited the contractile response induced by exogenously applied alpha, beta-MeATP (3 x 10(-7) to 10(-5) M.) but only slightly inhibited the contractile response induced by exogenously applied carbachol (3 x 10(-8) to 10(-6) M.).

CONCLUSION

These results suggest that YM934 may hyperpolarize the membrane of pig detrusor smooth muscle through the opening of ATP-sensitive potassium channels and, as a result, may functionally inhibit the contractile response to purinergic nerve stimulation that elicits the membrane depolarization.

摘要

目的

在离体猪逼尿肌平滑肌中研究钾通道开放剂YM934对兴奋性神经递质引起的收缩反应的影响。

材料与方法

电场刺激（EFS；5秒串刺激，50伏，持续时间0.8毫秒）、α,β-甲基ATP（3×10⁻⁷至10⁻⁵摩尔/升）或卡巴胆碱（3×10⁻⁸至10⁻⁶摩尔/升）可使离体猪逼尿肌平滑肌产生收缩反应。与假定的共递质乙酰胆碱和ATP的拮抗作用相比，评估YM934对收缩反应的影响。

结果

获得了对电场刺激的河豚毒素敏感、频率依赖性的收缩反应。阿托品（3×10⁻⁸摩尔/升）在高频时显著抑制收缩反应，而α,β-甲基ATP（5×10⁻⁶摩尔/升）（P2X嘌呤受体脱敏剂）在低频时显著抑制反应。YM934（10⁻⁸至10⁻⁷摩尔/升）剂量依赖性地抑制对所有频率的神经介导的收缩反应，但与α,β-甲基ATP类似，优先在低频时起作用。YM934（3×10⁻⁸摩尔/升）和阿托品（3×10⁻⁸摩尔/升）联合使用可使所有频率的反应降低至对照的10%至20%，这一效果与α,β-甲基ATP（5×10⁻⁶摩尔/升）和阿托品（3×10⁻⁸摩尔/升）联合使用时相似。此外，YM9