Biochemical and Pharmacological Characterization of Ganglionic Dopamine Receptors

Abstract

The presence and the subtype of dopamine receptors in sympathetic ganglia were investigated. Using dopamine as well as preferential agonists and antagonists for the DA-1 and DA-2 receptor subtypes, we have studied dopamine receptors in both dog and rat sympathetic ganglia. Dopamine, fenoldopam, a DA-1 receptor agonist, and quinpirole, a DA-2 receptor agonist, caused significant inhibition of ganglionic transmission. The inhibitory action of quinpirole was selectively antagonized by the DA-2 receptor antagonist S-sulpiride but not by the DA-1 receptor antagonist R-sulpiride. In contrast, the inhibition of ganglionic transmission produced by fenoldopam was antagonized by R-sulpiride but not S-sulpiride. The selective DA-1 receptor antagonist, SCH 23390 did not alter the inhibitory effect of fenoldopam at the ganglia. Dopamine and fenoldopam increased vascular but not ganglionic cyclic AMP. The increase in vascular cyclic AMP was antagonized by the DA-1 receptor antagonists SCH 23390 and R-sulpiride. Quinpirole caused a modest but significant decrease in ganglionic cyclic AMP, sensitive to blockade by S-sulpiride. These results show that dopamine and selective DA-1 and DA-2 receptor agonists inhibit ganglionic transmission by activating two distinct subtypes of dopamine receptors located on sympathetic ganglia.