title: Prejunctional inhibitory effect of a dopamine D-2 agonist, N-0437, on vascular adrenergic responses.
abstract: N-0437 [2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin], a potent and selective agonist for D-2 dopamine receptors, was used to investigate inhibitory prejunctional dopamine receptors in the rat tail artery and rabbit ear artery. N-0437 inhibited contractile responses to transmural nerve stimulation in a frequency dependent manner. Thus, N-0437 profoundly inhibited responses to nerve stimulation in the rat tail artery at a frequency of 1 Hz (ED50 = 1.6 nM), but had minimal effects when nerves were stimulated at 6 Hz. The D-1/D-2 dopamine agonist, apomorphine, exhibited a similar frequency dependent inhibitory effect but with less potency (ED50 = 30 nM at 1 Hz). In concentrations up to 1 microM, N-0437 had no effect on responses to exogenously applied norepinephrine, but N-0437 inhibited [3H] norepinephrine efflux induced by transmural stimulation. Inhibitory effects of N-0437 were blocked by the D-2 antagonist sulpiride but not by the D-1 antagonist SCH 23390. Furthermore, the selective D-1 agonist SKF 38393 did not inhibit vascular responses to adrenergic nerve stimulation. These data indicate that the inhibitory effects of N-0437 are via activation of D-2 dopamine receptors that inhibit norepinephrine release. Thus, N-0437 shows potency and selectivity of action for prejunctional D-2 dopamine receptors in vascular tissues. The frequency dependence of the actions of N-0437 suggest that the level of sympathetic activity is an important variable in determining effectiveness of prejunctional modulation.
authors.affiliation: Department of Pharmacology, College of Medicine, University of California, Irvine.
authors.forename: D J
authors.initials: DJ
authors.lastname: Friedman
authors.forename: D
authors.initials: D
authors.lastname: Budai
authors.forename: D N
authors.initials: DN
authors.lastname: Krause
authors.forename: S P
authors.initials: SP
authors.lastname: Duckles
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000818:Animals; D001158:Arteries / Q000294:innervation* / Q000502:physiology; D001552:Benzazepines / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists; D004558:Electric Stimulation; D066298:In Vitro Techniques; D009281:Naphthalenes / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects*; D013469:Sulpiride / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects; D014666:Vasomotor System / Q000502:physiology*
chemical_list: D001552:Benzazepines; D018492:Dopamine Antagonists; D009281:Naphthalenes; D011954:Receptors, Dopamine; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D013469:Sulpiride; C047508:rotigotine; D004298:Dopamine; D009638:Norepinephrine