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 Ki 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 microM, respectively. However, the EC50s of DA (3 microM) and the DA releasing drug amphetamine (1 microM) 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.