Dopamine displays an identical apparent affinity towards functional dopamine D1 and D2 receptors in rat striatal slices: Possible implications for the regulatory role of D2 receptors

In this study we examined the selectivity of dopamine (DA) for rat striatal DA D₁ and D₂ receptors. In a Krebs-HEPES buffer, the K_i values of DA for D₁ binding sites (labelled with ³H]SCH23390) and D₂ binding sites (labelled with ³H]spiroperidol) in striatal membranes amounted to about 30 and.0.3 μM, respectively. However, the EC50s of DA (3 μM) and the DA releasing drug amphetamine (1 μM) were identical considering D₁ receptor-stimulated and D₂ receptor-inhibited adenylate cyclase activity in superfused striatal slices. Moreover, these EC₅₀ values were also obtained studying DA- and amphetamine-induced D₂ receptor activation, resulting in inhibition of the electrically evoked release of ¹⁴C]acetylcholine from the slices. Therefore, with regard to the apparent affinity of exogenous and endogenous DA for D₁ and D₂ receptors in rat striatal slices, the ligand-receptor binding data appeared to be misleading. Thus, our data show that in rat striatal slices DA has an identical apparent affinity towards functional D₁ and D₂ receptors, which is particularly intriguing in view of the very high receptor selectivity of synthetic D₁ and D₂ receptor agonists for these functional receptors in superfused brain slices as predicted on the basis of binding assays. This may have important implications for our understanding of central DA neurotransmission. For instance, since the inhibitory effect of opioid and muscarinic receptor activation on adenylate cyclase activity has been shown to be inversely related to the degree of DA D₂ receptor activation, the degree of activation of D₁ and D₂ receptors by released DA is suggested to act as a functional gate allowing distinct neurotransmitters to play a role in striatal neurotransmission. © 1994 Wiley-Liss, Inc.