Noradrenaline and adrenaline are high affinity agonists at dopamine D sub(4) receptors

The activity of monoamine neurotransmitters was examined at dopamine D sub(4) receptors. In competition binding with [ super(3)H]spiperone, noradrenaline and adrenaline exhibited a high affinity binding component (K sub(H) = 12.1 nM and 5.0 nM, respectively), similar to that of dopamine (K sub(H) = 2.6 nM), whereas serotonin (5-hydroxytryptamine, 5-HT) and histamine had low affinity (K sub(i) > 1000 nM). Noradrenaline and adrenaline acted as agonists at dopamine D sub(4) receptors, stimulating receptor-mediated [ super(35)S]guanylyl- gamma -thiotriphosphane ([ super(35)S]GTP gamma S) binding (EC sub(50) = 7.8 and 5.8 mu M, respectively, versus 0.1 mu M for dopamine). The dopamine D sub(4) receptor-selective ligand 3-(4-[4-chlorophenyl]piperazin-1-yl)methyl-1 H-pyrrolo[2,3b]-pyridine (L 745,870) and the dopaminergic antagonists, spiperone, haloperidol and clozapine, inhibited noradrenaline-stimulated [ super(35)S]GTP gamma S binding whereas alpha sub(1)-, alpha sub(2)- and beta -adrenoceptor antagonists did not. These results indicate that dopamine D sub(4) receptors are activated by noradrenaline and adrenaline, although at 50-100-fold higher concentrations than dopamine.