Requirement for DARPP-32 in mediating effect of dopamine D2 receptor activation.

It is well documented that dopamine and dopamine D1 agonists convert the protein phosphatase-1 inhibitor, DARPP-32, from its dephosphorylated, inactive form into its Thr34-phosphorylated, active form, and that these effects on DARPP-32 constitute essential components of the mechanism by which dopamine and D1 agonists achieve their biological effects. In contrast to dopamine and D1 agonists, dopamine D2 agonists dephosphorylate and inactivate DARPP-32. Here we have examined the possibility that the biological effects of dopamine D2 receptor agonists might also involve DARPP-32. For this purpose, we have examined regulation of the activity of the electrogenic ion pump Na+,K+-ATPase, an established target for dopamine signalling. We have found that dopamine D1 agonists and dopamine D2 agonists inhibit Na+,K+-ATPase activity in dissociated cells from the mouse neostriatum and that, in each case, the effect is abolished in cells from mice deficient in DARPP-32. We conclude that DARPP-32 may play an obligatory role in dopaminergic signalling mediated both by D1 receptors and by D2 receptors.