Johri A M, Janssen L J
Asthma Research Group, Smooth Muscle Research Group, and the Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
J Pharmacol Exp Ther. 1999 Aug;290(2):847-53.
We set out to characterize the types of Ca(2+) channels that mediate release of the predominant excitatory (acetylcholine) and inhibitory (norepinephrine) neurotransmitters in canine bronchi, using electrically evoked contractions and relaxations, respectively, as indicators of this release. We found that the selective N-type Ca(2+) channel blocker (omega-conotoxin GVIA) eliminated electrically evoked contractions in a dose-dependent fashion (half-maximal inhibition in the presence of 1-5 nM) but had no significant effect on those evoked by exogenously added acetylcholine. Selective blockers of P-type Ca(2+) channels (omega-agatoxin TK; 10(-8) to 10(-7) M) or of L-type Ca(2+) channels (nifedipine; 10(-8) to 10(-6) M) had no significant effect on the responses to neurally released or exogenously added acetylcholine. Likewise, electrically evoked relaxations were blocked by omega-conotoxin GVIA (10(-7) M) but not by omega-agatoxin TK (10(-7) M) or nifedipine (10(-7) M); none of these Ca(2+) channel blockers had a significant inhibitory effect on isoproterenol-triggered relaxations. We conclude that excitatory and inhibitory neurotransmission in canine bronchi is mediated predominantly by N-type Ca(2+) channels, with little or no contribution from L-, P-, Q-, or T-type channels.
我们分别利用电诱发的收缩和舒张作为犬支气管中主要兴奋性（乙酰胆碱）和抑制性（去甲肾上腺素）神经递质释放的指标，着手对介导这些释放的钙通道类型进行表征。我们发现，选择性N型钙通道阻滞剂（ω-芋螺毒素GVIA）以剂量依赖性方式消除电诱发的收缩（在1 - 5 nM存在时半数最大抑制），但对外源性添加乙酰胆碱诱发的收缩无显著影响。P型钙通道（ω-阿加毒素TK；10⁻⁸至10⁻⁷ M）或L型钙通道（硝苯地平；10⁻⁸至10⁻⁶ M）的选择性阻滞剂对神经释放或外源性添加乙酰胆碱的反应无显著影响。同样，电诱发的舒张被ω-芋螺毒素GVIA（10⁻⁷ M）阻断，但未被ω-阿加毒素TK（10⁻⁷ M）或硝苯地平（10⁻⁷ M）阻断；这些钙通道阻滞剂对异丙肾上腺素引发的舒张均无显著抑制作用。我们得出结论，犬支气管中的兴奋性和抑制性神经传递主要由N型钙通道介导，L型、P型、Q型或T型通道贡献很小或无贡献。
