Myers P R, Livengood D R, Shain W
J Cell Physiol. 1977 Apr;91(1):103-18. doi: 10.1002/jcp.1040910111.
The physiology and pharmacology of a depolarizing dopamine response was studied in the vertebrate neuronal somatic cell hybrid TCX11. The average resting membrane potential was -50 mV (S.D.=+/-7) with a membrane resistance of 40.5 mOhms (S.D.=+/-8) as determined from intracellular recordings. Depolarizing current pulses did not elicit an action potential. Cells displayed a linear current-voltage relationship when artificially depolarized up to +30 mV. Iontophoretically applied dopamine elicited a depolarizing response with a conductance increase and a reversal potential of -15 mV (S.D.=+/-4.7). Experiments altering medium ion concentrations demonstrated the conductance increase was to sodium and most likely potassium. The dopamine agonist ET495 (Piribedil) and the analogue epinine mimicked dopamine, while closely related biogenic amines, with the exception of noradrenaline, elicited no response. Apomorphine also elicited a depolarizing response but was much less efficacious than Piribedil. Noradrenaline was less potent than dopamine and appeared to act at the dopamine receptor. Methylation (3-methoxytyramine) or absence of the 3-hydroxy group (tyramine) of dopamine resulted in total loss of activity. The dopamine antagonists chlorpromazine, trifluoperazine, promazine, and bulbocapnine reversibly blocked the response to dopamine at medium concentrations less than 5 micronM. The adrenergic antagonist phentolamine blocked the response while phenoxybenzamine only reduced the response at higher concentrations. The acetylcholine antagonists alpha-bungarotoxin, hexamethonium, and scopolamine did not block the dopamine response. Both d-tubocurarine and atropine acted as antagonists. Collectively, these results demonstrate the presence of a receptor on a cultured cell line that is specific for dopamine, mediates a depolarizing and conductance increase response to dopamine, and displays the pharmacology most closely associated with dopamine receptors.
在脊椎动物神经元体细胞杂交体TCX11中研究了去极化多巴胺反应的生理学和药理学特性。通过细胞内记录测定，平均静息膜电位为-50 mV（标准差=±7），膜电阻为40.5毫欧（标准差=±8）。去极化电流脉冲未引发动作电位。当人工将细胞去极化至+30 mV时，细胞呈现线性电流-电压关系。离子电泳施加多巴胺可引发去极化反应，电导增加，反转电位为-15 mV（标准差=±4.7）。改变培养基离子浓度的实验表明，电导增加是针对钠离子，很可能还有钾离子。多巴胺激动剂ET495（匹莫齐特）和类似物去甲肾上腺素能模仿多巴胺，而除去甲肾上腺素外的密切相关生物胺未引发反应。阿扑吗啡也引发去极化反应，但效力远低于匹莫齐特。去甲肾上腺素的效力低于多巴胺，似乎作用于多巴胺受体。多巴胺的甲基化（3-甲氧基酪胺）或3-羟基缺失（酪胺）导致活性完全丧失。多巴胺拮抗剂氯丙嗪、三氟拉嗪、丙嗪和白屈菜红碱在浓度低于5微摩尔时可可逆地阻断对多巴胺的反应。肾上腺素能拮抗剂酚妥拉明可阻断该反应，而酚苄明仅在较高浓度时降低反应。乙酰胆碱拮抗剂α-银环蛇毒素、六甲铵和东莨菪碱不阻断多巴胺反应。d-筒箭毒碱和阿托品均起拮抗剂作用。总体而言，这些结果表明在一种培养细胞系上存在一种对多巴胺特异的受体，介导对多巴胺的去极化和电导增加反应，并表现出与多巴胺受体最密切相关的药理学特性。
