Pharmacological characterization of Dopamine receptors in the sympathetic ganglia

Two pharmacologically distinct dopamine receptors are shown to exist in the periphery. The vascular dopamine receptor which mediates regional vasodilation represents the DA-I subtype, whereas the presynaptic dopamine receptor present on postganglionic sympathetic nerve terminal and which causes inhibition of the stimulation-evoked neurotransmitter release, is termed the DA-2 receptor. Although dopamine is reported to inhibit ganglionic transmission, the receptor mediating the action of dopamine has not been identified. The present study was designed to characterize ganglionic dopamine receptor by employing selective agonists and antagonists. In anesthetized dogs, the DA-I receptor agonist, fenoldopam, caused hypotension and significant inhibition of tachycardia elicited during preganglionic but not postganglionic stellate stimulation, suggesting that this compound depressed transmission across the ganglia. These actions were antagonized by the dopamine receptor antagonists R-sulpiride and metoclopramide but not by the preferential DA-2 receptor antagonist, 5-sulpiride. However, the more selective and potent DA-I receptor antagonist, SCH 23390, failed to alter the ganglionic inhibitory action of fenoldopam, although it was more potent than R-sulpiride and metoclopramide in antagonizing the hypotension. Fenoldopam infusion to anesthetized dogs also caused significant impairment of hindlimb vasoconstriction produced by preganglionic lumbar sympathetic nerve stimulation. The inhibitory action of fenoldopam was antagonized by R-sulpiride but not by SCH 23390, although SCH 23390 was more effective than R-sulpiride in antagonizing the hypotensive action of fenoldopam. In the electrophysiological experiments performed on isolated dog stellate and rat superior cervical ganglia fenoldopam produced concentration-dependent inhibition of ganglionic transmission. This was evident in the decrease in the amplitude of compound postganglionic action potential evoked by preganglionic nerve stimulation. Whereas R-sulpiride and metoclopramide antagonized this inhibitory action of fenoldopam on ganglionic transmission, S-sulpiride, SCH 23390 and Phentolamine were ineffective. In anesthetized dogs, the selective DA-2 receptor agonist, quinpirole, produced hypotension and inhibition of tachycardia elicited during preganglionic as well as postganglionic stellate Stimulaton. These two actions were significantly antagonized by RS-sulpiride. In the isolated stellate ganglion of the dog and superior cervical ganglion of the rat, quinpirole produced concentration-dependent inhibition of ganglionic transmission which was antagonized by S-sulpiride but not R-sulpiride. In electrophysiological experiments performed on dog stellate and rat superior cervical ganglia, dopamine caused a concentration-dependent inhibition of ganglionic transmission. This inhibitory action of dopamine was antagonized by either R-sulpiride or S-sulpiride but not by SCH 23390. In biochemical studies in the isolated dog stellate and rat superior cervical ganglia, neither dopamine nor fenoldopam caused any significant changes in cyclic AMP, whereas isoproterenol produced marked increases in cyclic AMP content. Quinpirole produced a modest but significant decrease in cyclic AMP in stellate ganglia which was antagonized by S-sulpiride. In renal arteries of the dog and the rat, both dopamine and fenoldopam produced significant increases in cyclic AMP levels. Preincubation with R-sulpiride and SCH 23390 prevented these effects of dopamine and fenoldopam. These findings show the presence of two distinct subtypes of dopamine receptors in sympathetic ganglia, activation of which produces inhibition of ganglionic transmission. The dopamine receptor which mediates the ganglionic inhibitory action of quinpirole appears to be similar to the presynaptic dopamine (DA-2) receptor. However, the receptor involved in the ganglionic inhibitory action of fenoldopam exhibits some differences from the vascular DA-I receptor.