Dopamine displays an identical apparent affinity towards functional dopamine D 1 and D 2 receptors in rat striatal slices: Possible implications for the regulatory role of D 2 receptors

In this study we examined the selectivity of dopamine (DA) for rat striatal DA D 1 and D 2 receptors. In a Krebs‐HEPES buffer, the K i values of DA for D 1 binding sites (labelled with [ 3 H]SCH23390) and D 2 binding sites (labelled with [ 3 H]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 D 1 receptor‐stimulated and D 2 receptor‐inhibited adenylate cyclase activity in superfused striatal slices. Moreover, these EC 50 values were also obtained studying DA‐ and amphetamine‐induced D 2 receptor activation, resulting in inhibition of the electrically evoked release of [ 14 C]acetylcholine from the slices. Therefore, with regard to the apparent affinity of exogenous and endogenous DA for D 1 and D 2 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 D 1 and D 2 receptors, which is particularly intriguing in view of the very high receptor selectivity of synthetic D 1 and D 2 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 D 2 receptor activation, the degree of activation of D 1 and D 2 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.