Dopaminergic and alpha-adrenergic control of neurotransmission in human right atrium.
The aim of the present study was to investigate dopamine receptor- and alpha-adrenergic receptor-mediated modulation of norepinephrine release in human atria. Right atrial appendages were incubated with 3H-norepinephrine, placed in superfusion chambers, and field-stimulated by platinum electrodes at a frequency of 5 Hz. The stimulation-induced (S-I) outflow of radioactivity was taken as an index of norepinephrine release. The dopamine D2-receptor agonist quinpirole (0.03-3 microM) concentration dependently inhibited the S-I outflow of radioactivity with an EC50 of 0.03 microM. The concentration-response curve of quinpirole was potently shifted to the right by the D2-receptor antagonists domperidone (0.003 microM, pKB approximately 9.2) and S(-)-sulpiride (0.1 microM, pKB approximately 8.6). The D1-receptor antagonist SCH 23390 (1 microM) slightly (pKB approximately 6.9) shifted the concentration-response curve of quinpirole, whereas the alpha 2-adrenergic antagonist rauwolscine (0.01 microM) and the alpha 1-adrenergic antagonist prazosin (1 microM) had no effect. The D1-receptor agonist did not affect fenoldopam (0.03 and 0.3 microM), but fenoldopam (3 microM) enhanced the S-I outflow of radioactivity. The facilitatory effect of fenoldopam (3 microM) was unaltered by SCH 23390 (0.1 microM) but prevented by rauwolscine (0.01 microM). The alpha 2-adrenergic agonist UK 14304 (0.01-1 microM) (EC50: 0.06 microM), but not the alpha 1-adrenergic agonist methoxamine (0.3-30 microM), inhibited S-I outflow of radioactivity. The concentration-response curve of UK 14304 was shifted to the right by rauwolscine (0.01 microM, pKB approximately 8.6).(ABSTRACT TRUNCATED AT 250 WORDS)
Rump
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LC
Universitätsklinik Freiburg, Innere Medizin IV, Freiburg, Germany.
Riera-Knorrenschild
G
G
Schwertfeger
E
E
Bohmann
C
C
Spillner
G
G
Schollmeyer
P
P
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D001552:Benzazepines / Q000494:pharmacology; D000068438:Brimonidine Tartrate; D004294:Domperidone / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004558:Electric Stimulation; D004873:Ergolines / Q000494:pharmacology; D005260:Female; D018818:Fenoldopam / Q000494:pharmacology; D006325:Heart Atria / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism; D011224:Prazosin / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D019257:Quinpirole; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D013469:Sulpiride / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D004873:Ergolines; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D011954:Receptors, Dopamine; D019257:Quinpirole; D015016:Yohimbine; D000068438:Brimonidine Tartrate; D004294:Domperidone; D013469:Sulpiride; D008729:Methoxamine; D018818:Fenoldopam; D009638:Norepinephrine; D011224:Prazosin