Mu- and delta-opioid receptor agonists inhibit DARPP-32 phosphorylation in distinct populations of striatal projection neurons.
In the striatum, DARPP-32 (dopamine- and cAMP-regulated phosphoprotein of 32 kDa) is highly expressed by virtually all projection medium-sized spiny neurons. cAMP-dependent phosphorylation of DARPP-32 is stimulated via activation of dopamine D1 receptors in striatonigral neurons, and via activation of adenosine A2A receptors in striatopallidal neurons. In this study, we have examined the contribution of mu-, delta- and kappa-opioid receptors to the regulation of DARPP-32 phosphorylation, in rat striatal slices. The results show that, at low concentrations (100 pm-1 nm), the mu-opioid agonist, Tyr-D-Ala-Gly-N-Me-Phe-glycinol (DAMGO), inhibits the increase in DARPP-32 phosphorylation induced by activation of D1, but not by activation of A2A receptors. Conversely, the delta-receptor agonist, Tyr-D-Pen-Gly-Phe-D-Pen (DPDPE), inhibits DARPP-32 phosphorylation induced by activation of A2A, but not by activation of D1 receptors. The kappa-receptor agonist, U50488, does not affect DARPP-32 phosphorylation induced by either D1 or A2A agonists. Thus, mu-opioid receptors interact with dopamine D1 receptors on striatonigral neurons, whereas delta-opioid receptors interact with adenosine A2A receptors on striatopallidal neurons. These results suggest that regulation of DARPP-32 phosphorylation is involved in mediating some of the effects exerted by enkephalin on striatal medium-sized spiny neurons.
Lindskog
M
M
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Svenningsson
P
P
Fredholm
B
B
Greengard
P
P
Fisone
G
G
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism*; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010750:Phosphoproteins; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000819:agonists*; D017450:Receptors, Opioid, mu / Q000819:agonists*
D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D004745:Enkephalins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D015124:8-Bromo Cyclic Adenosine Monophosphate; D016202:N-Methylaspartate; D020881:Enkephalin, D-Penicillamine (2,5)-