Dopamine receptors in the stellate ganglion of the dog.
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.
Kohli
J D
JD
Department of Pharmacological and Physiological Sciences, University of Chicago, IL 60637.
Metra
M
M
Satoh
Y
Y
Goldberg
L I
LI
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D000068438:Brimonidine Tartrate; D004285:Dogs; D015259:Dopamine Agents / Q000494:pharmacology; D004558:Electric Stimulation; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008297:Male; D011810:Quinoxalines / Q000494:pharmacology; D011954:Receptors, Dopamine / Q000378:metabolism*; D013233:Stellate Ganglion / Q000378:metabolism* / Q000502:physiology
D000959:Antihypertensive Agents; D015259:Dopamine Agents; D011810:Quinoxalines; D011954:Receptors, Dopamine; D000068438:Brimonidine Tartrate