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μ‐ and δ‐opioid receptor agonists inhibit DARPP‐32 phosphorylation in distinct populations of striatal projection neurons
Author(s) -
Lindskog Maria,
Svenningsson Per,
Fredholm Bertil,
Greengard Paul,
Fisone Gilberto
Publication year - 1999
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.1999.00597.x
Subject(s) - adenosine a2a receptor , medium spiny neuron , damgo , δ opioid receptor , chemistry , agonist , receptor , enkephalin , dopamine receptor d1 , phosphorylation , dopamine , κ opioid receptor , dopamine receptor , medicine , neuroscience , endocrinology , striatum , opioid , opioid receptor , biology , adenosine receptor , biochemistry
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 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 μ‐, δ‐ and κ‐opioid receptors to the regulation of DARPP‐32 phosphorylation, in rat striatal slices. The results show that, at low concentrations (100 p m –1 n m ), the μ‐opioid agonist, 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 δ‐receptor agonist, Tyr‐D‐Pen‐Gly‐Phe‐D‐Pen (DPDPE), inhibits DARPP‐32 phosphorylation induced by activation of A 2A , but not by activation of D 1 receptors. The κ‐receptor agonist, U50488, does not affect DARPP‐32 phosphorylation induced by either D 1 or A 2A agonists. Thus, μ‐opioid receptors interact with dopamine D 1 receptors on striatonigral neurons, whereas δ‐opioid receptors interact with adenosine A 2A 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.