Pharmacological characterization of dopamine receptors in the stellate ganglia with selective DA1 and DA2 receptor agonists and antagonists

Abstract

Experiments were performed with fenoldopam (SKF-82526), a selective DA1 receptor agonist, and quinpirole (LY-171555), a selective DA2 receptor agonist, to determine their actions on ganglionic transmission. Fenoldopam caused significant inhibition of the tachycardia elicited during preganglionic stellate stimulation; however, it did not alter the positive chronotropic responses to postganglionic stellate stimulation, suggesting that the compound exerts its inhibitory action at the ganglia. Electrophysiological experiments in the isolated stellate ganglia showed that fenoldopam produced inhibition of ganglionic transmission as indicated by a significant reduction in the magnitude of the compound postganglionic action potential elicited during preganglionic nerve stimulation. The inhibition of ganglionic transmission produced by fenoldopam both under in vivo and in vitro conditions was antagonized by R-sulpiride and metoclopramide, but not by SCH 23390, S-sulpiride or phentolamine. Quinpirole produced significant inhibition of the tachycardia elicited during both preganglionic as well as postganglionic cardiac sympathetic nerve stimulation. This action of quinpirole was antagonized by RS-sulpiride. In electrophysiological experiments it was discovered that quinpirole caused a significant reduction in the magnitude of the compound action potential elicited during stimulation of preganglionic stellate nerve fibers. This inhibition of ganglionic transmission produced by quinpirole was antagonized by S- but not by R-sulpiride. Although phentolamine antagonized the inhibitory action of quinpirole, it was much less effective than S-sulpiride. Norepinephrine also produced inhibition of ganglionic transmission in the isolated stellate ganglia which was antagonized by phentolamine but not by S-sulpiride. These results demonstrate the presence of two subtypes of specific dopamine receptors in the stellate ganglia.(ABSTRACT TRUNCATED AT 250 WORDS)