Prejunctional inhibitory effect of a dopamine D-2 agonist, N-0437, on vascular adrenergic responses

D. J. Friedman, D. Budai, D. N. Krause, S. P. Duckles

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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 μM, 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 levels of sympathetic activity is an important variable in determining effectiveness of prejunctional modulation.

Original languageEnglish
Pages (from-to)853-859
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume250
Issue number3
Publication statusPublished - 1989

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Adrenergic Agents
Blood Vessels
Dopamine
Dopamine Receptors
Norepinephrine
Arteries
Tail
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
N 0437
Sulpiride
Apomorphine
Dopamine Agonists
Ear
Rabbits

ASJC Scopus subject areas

  • Pharmacology

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Prejunctional inhibitory effect of a dopamine D-2 agonist, N-0437, on vascular adrenergic responses. / Friedman, D. J.; Budai, D.; Krause, D. N.; Duckles, S. P.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 250, No. 3, 1989, p. 853-859.

Research output: Contribution to journalArticle

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