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

It is well documented that dopamine and dopamine D1 agonists convert the pr otein phosphatase-1 inhibitor, DARPP-32, from its dephosphorylated, inactiv e form into its Thr(34)-phosphorylated, active form, and that these effects on DARPP-32 constitute essential components of the mechanism by which dopa mine and D1 agonists achieve their biological effects. In contrast to dopam ine and D1 agonists, dopamine D2 agonists dephosphorylate and inactivate DA RPP-32. Here we have examined the possibility that the biological effects o f dopamine D2 receptor agonists might also involve DARPP-32. For this purpo se, we have examined regulation of the activity of the electrogenic ion pum p Na+,K+-ATPase, an established target for dopamine signalling. We have fou nd 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 signall ing mediated both by D1 receptors and by D2 receptors.