mu- and delta-opioid receptor agonists inhibit DARPP-32 phosphorylation indistinct populations of striatal projection neurons

In the striatum, DARPP-32 (dopamine- and cAMP-regulated phosphoprotein of 3 2 kDa) is highly expressed by virtually all projection medium-sized spiny n eurons. cAMP-dependent phosphorylation of DARPP-32 is stimulated via activa tion of dopamine D-1 receptors in striatonigral neurons, and via activation of adenosine A(2A) receptors in striatopallidal neurons, In this study, we have examined the contribution of mu-, delta- and kappa-opioid receptors t o the regulation of DARPP-32 phosphorylation, in rat striatal slices. The r esults show that, at low concentrations (100 pM-1 nM), the mu-opioid agonis t, Tyr-D-Ala-Gly-N-Me-Phe-glycinol (DAMGO), inhibits the increase in DARPP- 32 phosphorylation induced by activation of D-1, but not by activation of A (2A) receptors, Conversely, the delta-receptor agonist, Tyr-D-Pen-G ly-Phe- D-Pen (DPDPE), inhibits DARPP-32 phosphorylation induced by activation of A (2A), but not by activation of D-1 receptors, The kappa-receptor agonist, U 50488, does not affect DARPP-32 phosphorylation induced by either D-1 or A( 2A) agonists. Thus, mu-opioid receptors interact with dopamine D-1 receptor s on striatonigral neurons, whereas delta-opioid receptors interact with ad enosine A(2A) receptors on striatopallidal neurons. These results suggest t hat regulation of DARPP-32 phosphorylation is involved in mediating some of the effects exerted by enkephalin on striatal medium-sized spiny neurons.