Uchida W, Masuda N, Shirai Y, Shibasaki K, Satoh N, Takenada T
Cardiovascular and Atherosclerosis Research Laboratories, Yamanouchi Institute for Drug Discovery Research, Ibaraki, Japan.
Naunyn Schmiedebergs Arch Pharmacol. 1994 Oct;350(4):398-402. doi: 10.1007/BF00178958.
The role of extracellular Ca2+ in the tonic-contractile response to muscarinic receptor stimulation was investigated in isolated detrusor smooth muscle from the pig urinary bladder. Carbachol (10(-8)-10(-5) M) produced a concentration-dependent contractile response in isolated pig detrusor smooth muscle strips consisting of an initial phasic component followed by a tonic component. During the plateau of the tonic contractions induced by carbachol at the submaximal concentration of 10(-6) M, the inhibiting effects of atropine, EGTA, nifedipine (a voltage-dependent calcium channel antagonist), H-7 [a protein kinase C (PKC) inhibitor] and YM934 (a potassium channel opener) on the contractions were evaluated. Atropine (10(-10)-3 x 10(-8) M) concentration-dependently inhibited the tonic contractions induced by carbachol. In the same experimental conditions, EGTA (4 mM) and nifedipine (10(-9)-3 x 10(-7) M) depressed the tonic contractions in a concentration-dependent manner as did H-7 (10(-5)-3 x 10(-5) M) and YM934 (10(-8)-10(-6) M). However, H-7 (10(-5)-3 x 10(-5) M) and YM934 (10(-6) M) were very weak in inhibiting the contractions induced by KCl (50 mM) in isolated pig detrusor smooth muscle strips. These results suggest that the tonic-contractile response induced by carbachol in pig detrusor smooth muscle strips is dependent mainly on depolarization of the cell membranes and an influx of extracellular Ca2+, and also suggest that this depolarizing response may be due to inactivation of ATP-sensitive potassium channels through muscarinic activation of PKC.
在猪膀胱分离的逼尿肌平滑肌中，研究了细胞外钙离子在毒蕈碱受体刺激引起的强直性收缩反应中的作用。卡巴胆碱（10^(-8)-10^(-5)M）在分离的猪逼尿肌平滑肌条中产生浓度依赖性收缩反应，包括初始的相性成分和随后的强直性成分。在卡巴胆碱以10^(-6)M的次最大浓度诱导强直性收缩的平台期，评估了阿托品、乙二醇双四乙酸（EGTA）、硝苯地平（一种电压依赖性钙通道拮抗剂）、H-7[一种蛋白激酶C（PKC）抑制剂]和YM934（一种钾通道开放剂）对收缩的抑制作用。阿托品（10^(-10)-3×10^(-8)M）浓度依赖性地抑制卡巴胆碱诱导的强直性收缩。在相同的实验条件下，EGTA（4mM）和硝苯地平（10^(-9)-3×10^(-7)M）以浓度依赖性方式抑制强直性收缩，H-7（10^(-5)-3×10^(-5)M）和YM934（10^(-8)-10^(-6)M）也是如此。然而，H-7（10^(-5)-3×10^(-5)M）和YM934（10^(-6)M）在抑制分离的猪逼尿肌平滑肌条中由氯化钾（50mM）诱导的收缩方面非常微弱。这些结果表明，卡巴胆碱在猪逼尿肌平滑肌条中诱导的强直性收缩反应主要依赖于细胞膜的去极化和细胞外钙离子的内流，并且还表明这种去极化反应可能是由于PKC的毒蕈碱激活导致ATP敏感性钾通道失活所致。
