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.
Nishi
A
A
Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, 10021-6390, USA.
Snyder
G L
GL
Fienberg
A A
AA
Fisone
G
G
Aperia
A
A
Nairn
A C
AC
Greengard
P
P
D000818:Animals; D018491:Dopamine Agonists / Q000494:pharmacology; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D018818:Fenoldopam / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000502:physiology; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D010750:Phosphoproteins; D019257:Quinpirole / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism
D018491:Dopamine Agonists; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D000254:Sodium-Potassium-Exchanging ATPase; D018818:Fenoldopam