Noradrenaline and adrenaline are high affinity agonists at dopamine D4 receptors.
The activity of monoamine neurotransmitters was examined at dopamine D4 receptors. In competition binding with [3H]spiperone, noradrenaline and adrenaline exhibited a high affinity binding component (KH = 12.1 nM and 5.0 nM, respectively), similar to that of dopamine (KH = 2.6 nM), whereas serotonin (5-hydroxytryptamine, 5-HT) and histamine had low affinity (Ki > 1000 nM). Noradrenaline and adrenaline acted as agonists at dopamine D4 receptors, stimulating receptor-mediated [35S]guanylyl-gamma-thiotriphosphate ([35S]GTP gamma S) binding (EC50 = 7.8 and 5.8 microM, respectively, versus 0.1 microM for dopamine). The dopamine D4 receptor-selective ligand, 3-(4-[4-chlorophenyl]piperazin-1-yl)methyl-1H-pyrrolo[2,3b]-pyridi ne (L 745,870) and the dopaminergic antagonists, spiperone, haloperidol and clozapine, inhibited noradrenaline-stimulated [35S]GTP gamma S binding whereas alpha 1-, alpha 2- and beta-adrenoceptor antagonists did not. These results indicate that dopamine D4 receptors are activated by noradrenaline and adrenaline, although at 50-100-fold higher concentrations than dopamine.
Newman-Tancredi
A
A
Department of Psychopharmacology, Institut de Recherches Servier, Croissy-sur-Seine, Paris, France. 101511,274@compuserve.com
Audinot-Bouchez
V
V
Gobert
A
A
Millan
M J
MJ
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D016466:CHO Cells; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D006224:Cricetinae; D018491:Dopamine Agonists / Q000494:pharmacology*; D004837:Epinephrine / Q000494:pharmacology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D009638:Norepinephrine / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D050638:Receptors, Dopamine D4; D013462:Sulfur Radioisotopes; D013816:Thermodynamics
C099630:3-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-1H-pyrrolo(2,3-b)pyridine; C493599:DRD4 protein, human; D018491:Dopamine Agonists; D008024:Ligands; D011725:Pyridines; D011758:Pyrroles; D017448:Receptors, Dopamine D2; D013462:Sulfur Radioisotopes; D050638:Receptors, Dopamine D4; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D009638:Norepinephrine; D004837:Epinephrine