Steinsland O S, Furchgott R F
J Pharmacol Exp Ther. 1975 Apr;193(1):128-37.
In the perfused isolated central ear artery of the rabbit, nicotine, acetylcholine (ACh), tetramethylammonium (TMA) and carbachol (CCh) at high concentrations (greater than 1 mug/ml) produced transient vasoconstriction. The order of potency was: nicotine greater than ACh greater than TMA greater than CCh. Over the concentration range used, all of the agonists except ACh gave bell-shaped log concentration-response curves. Methacholine did not cause vasoconstriction. The response to ACh, TMA or CCh, but not to nicotine, was potentiated by atropine (0.1-1.0 mug/ml). Tetraethylammonium, hexamethonium, mecamylamine and d-tubocurarine blocked the response to the nicotinic agonists and to nerve stimulation. Ear arteries from reserpine-treated rabbits gave no, or very little, constrictor response to the nicotinic agonists or to nerve stimulation. These findings support the conclusion that the vasoconstriction produced by the nicotinic agonists is mediated by norepinephrine released from adrenergic nerve terminals as a result of the action of the agents on neuronal nicotinic receptors located at or near the terminals. The potentiation by atropine of the constrictor response to ACh, TMA and CCh is attributed to the blockade by atropine of neuronal muscarinic receptors on which these agonists act to inhibit the release of norepinephrine.
在兔离体灌注的中耳动脉中，尼古丁、乙酰胆碱（ACh）、四甲铵（TMA）和高浓度（大于1微克/毫升）的卡巴胆碱（CCh）可引起短暂的血管收缩。效力顺序为：尼古丁＞ACh＞TMA＞CCh。在所使用的浓度范围内，除ACh外，所有激动剂均呈现钟形的对数浓度-反应曲线。醋甲胆碱不引起血管收缩。阿托品（0.1 - 1.0微克/毫升）可增强对ACh、TMA或CCh的反应，但对尼古丁的反应无增强作用。四乙铵、六甲铵、美加明和d - 筒箭毒碱可阻断对烟碱激动剂和神经刺激的反应。利血平处理过的兔的耳动脉对烟碱激动剂或神经刺激无收缩反应或仅有非常微弱的收缩反应。这些发现支持这样的结论，即烟碱激动剂引起的血管收缩是由肾上腺素能神经末梢释放的去甲肾上腺素介导的，这源于这些药物作用于位于神经末梢或其附近的神经元烟碱受体。阿托品对ACh、TMA和CCh收缩反应的增强作用归因于阿托品对神经元毒蕈碱受体的阻断，这些激动剂作用于该受体以抑制去甲肾上腺素的释放。
