Gillespie J S, Tilmisany A K
Br J Pharmacol. 1976 Sep;58(1):47-55. doi: 10.1111/j.1476-5381.1976.tb07692.x.
1 Tetraethylammonium chloride (TEA) 0.125 mM to 20 mM potentiates the response of the anococcygeus muscle to field stimulation of the motor adrenergic nerves without affecting the response to noradrenaline suggesting a pre-synaptic origin of potentiation. The potentiation is greatest at low, submaximal, frequencies (2 Hz) of stimulation and only slight at the higher frequency of 20 Hz. This difference is due to the restraint imposed on the demonstration of potentiation by maximal or near maximal motor responses since reduction of the mechanical response at 20 Hz by either phentolamine (post-synaptic block) or guanethidine (pre-synaptic block) resulted in a great increase in potentiation of the response at this frequency. 2 TEA in concentrations up to 1 mM similarly potentites the response to inhibitory nerve stimulation and again the greatest effect is at low frequencies. Higher concentrations (5-20 mM) progressively depress the inhibitory response. It is suggested that TEA may specifically antagonize the post-synaptic action of the inhibitory transmitter and that at higher concentrations of TEA this effect dominates the pre-synaptic action in increasing transmitter release. 3 TEA has no effect on the motor response to tyramine. 4 TEA (5-20 mM) causes a maintained rise in muscle tone. Part of this is abolished by phentolamine but part is resistant. A similar muscle stimulant action of TEA is observed in muscles from rats previously treated with 6-hydroxydopamine in which indirect sympathomimetic drugs and field stimulation could no longer produce a motor response. These results suggest that part of the motor effect of TEA is due to an increased spontaneous release of noradrenaline and part to a direct action on the muscle. 5 TEA 0.125 mM to 20 mM antagonize the stimulant action of carbachol. Dose-response curves show a parallel shift to the right with no change in the maximum response suggesting a competitive atropine-like action. Such an effect has previously been reported in amphibian tissue but not so far as we can determine in mammalian preparations. 6 The possible mode of action of TEA is discussed.
0.125毫摩尔至20毫摩尔的氯化四乙铵（TEA）增强了尾骨肌对运动肾上腺素能神经场刺激的反应，而不影响对去甲肾上腺素的反应，提示增强作用源于突触前。在低的、次最大频率（2赫兹）刺激时增强作用最大，在20赫兹的较高频率时则很轻微。这种差异是由于最大或接近最大运动反应对增强作用的显示施加了限制，因为用酚妥拉明（突触后阻断）或胍乙啶（突触前阻断）降低20赫兹时的机械反应会导致该频率下反应增强作用大幅增加。
浓度高达1毫摩尔的TEA同样增强了对抑制性神经刺激的反应，且最大效应同样出现在低频。更高浓度（5 - 20毫摩尔）逐渐抑制抑制性反应。提示TEA可能特异性拮抗抑制性递质的突触后作用，且在较高浓度的TEA时，这种作用在增加递质释放的突触前作用中占主导。
TEA对酪胺的运动反应无影响。
TEA（5 - 20毫摩尔）使肌张力持续升高。部分升高被酚妥拉明消除，但部分有抗性。在用6 - 羟基多巴胺预处理的大鼠肌肉中观察到TEA有类似的肌肉刺激作用 , 在此类肌肉中，间接拟交感神经药物和场刺激不再能产生运动反应。这些结果提示TEA的部分运动效应是由于去甲肾上腺素自发释放增加，部分是由于对肌肉的直接作用。
浓度为0.125毫摩尔至20毫摩尔的TEA拮抗卡巴胆碱的刺激作用。剂量 - 反应曲线显示平行右移，最大反应无变化，提示有竞争性的阿托品样作用。此前在两栖类组织中曾报道过这种效应，但据我们所知，在哺乳动物制剂中尚未有此报道。
讨论了TEA可能的作用方式。
