Kohli J D, Metra M, Satoh Y, Goldberg L I
Department of Pharmacological and Physiological Sciences, University of Chicago, IL 60637.
Eur J Pharmacol. 1989 May 19;164(2):265-72. doi: 10.1016/0014-2999(89)90467-6.
Effects of fenoldopam, a selective DA1 dopamine receptor agonist, and dipropyl dopamine and propylphenethyl dopamine, preferential DA2 dopamine receptor agonists, on ganglion transmission were studied in pentobarbital-anesthetized, open-chest dogs. Tachycardia induced by electrical stimulation (supramaximal voltage, 0.5 ms duration, 1-2 Hz) of the preganglionic cardio-accelerator nerves was monitored as a measure of ganglionic transmission. Drugs were injected into the costocervical artery (i.a.) close to the arterial supply of the ganglion. Doses required to produce 30-40% inhibition of ganglionic transmission by the i.a. route were 2-8 micrograms for dipropyl dopamine, 4-16 micrograms for propylphenethyl dopamine, and 100 micrograms for fenoldopam. At these doses none of the agonists affected tachycardia induced by electrical stimulation of the postganglionic nerve. Domperidone (5 micrograms/kg i.v.), a selective DA2 dopamine receptor antagonist, markedly antagonized the effects of dipropyl dopamine and propylphenethyl dopamine, but had only minor (and statistically insignificant) effects on the inhibitory effect of fenoldopam. SCH 23390 (5 micrograms/kg i.v.), a selective and potent DA1 antagonist, failed to modify the effects of any of the agonists. In a separate series, infusion of fenoldopam, 20 micrograms/kg per min i.v. for 5-7 min, facilitated postganglionic nerve stimulation and blocked the inhibitory effect of UK 14,304, an alpha 2-adrenoceptor agonist, on the postganglionic nerve. These results confirm and support the presence of DA2 but do not support the presence of the prototypal DA1 dopamine receptor in the mammalian ganglia. Furthermore, the alpha 2-adrenoceptor blocking property of fenoldopam points to the complication of using i.v. administration for studying its ganglionic actions while monitoring the target tissue effects in response to preganglionic nerve stimulation.
在戊巴比妥麻醉、开胸的犬身上，研究了选择性DA1多巴胺受体激动剂非诺多泮以及优先作用于DA2多巴胺受体的激动剂二丙基多巴胺和丙基苯乙胺对神经节传递的影响。通过对节前心脏加速神经进行电刺激（超最大电压，持续时间0.5毫秒，频率1 - 2赫兹）诱导的心动过速被监测，以此作为神经节传递的一种测量指标。药物经颈总动脉（动脉内）注入，此处靠近神经节的动脉供应。经动脉内途径产生30 - 40%神经节传递抑制所需的剂量，二丙基多巴胺为2 - 8微克，丙基苯乙胺为4 - 16微克，非诺多泮为100微克。在这些剂量下，没有一种激动剂影响节后神经电刺激诱导的心动过速。多潘立酮（静脉注射5微克/千克），一种选择性DA2多巴胺受体拮抗剂，显著拮抗二丙基多巴胺和丙基苯乙胺的作用，但对非诺多泮的抑制作用仅有轻微（且无统计学意义）影响。SCH 23390（静脉注射5微克/千克），一种选择性强效DA1拮抗剂，未能改变任何一种激动剂的作用。在另一个系列实验中，以每分钟20微克/千克的速度静脉输注非诺多泮5 - 7分钟，促进了节后神经刺激，并阻断了α2肾上腺素能受体激动剂UK 14,304对节后神经的抑制作用。这些结果证实并支持了哺乳动物神经节中存在DA2，但不支持存在典型的DA1多巴胺受体。此外，非诺多泮的α2肾上腺素能受体阻断特性表明，在监测节前神经刺激引起的靶组织效应时，静脉给药用于研究其神经节作用存在复杂性。
