Our previous studies showed that dopamine inhibits Na+,K+-ATPase activity i
n acutely dissociated neurons from striatum. In the present study, we have
found that in this preparation, dopamine inhibited significantly (by simila
r to 25%) the activity of the alpha 3 and/or alpha 2 isoforms, but not the
alpha 1 isoform, of Na+,K+-ATPase. Dopamine, via D1 receptors, activates cy
clic AMP-dependent protein kinase (PKA) in striatal neurons. Dopamine is al
so known to activate the calcium- and phospholipid-dependent protein kinase
(PKC) in a number of different cell types. The PKC activator phorbol 12,13
-dibutyrate reduced the activity of Na+,K+-ATPase alpha 3 and/or alpha 2 is
oforms (by similar to 30%) as well as the alpha 1 isoform (by similar to 15
%). However, dopamine-mediated inhibition of Na+,K+-ATPase activity was una
ffected by calphostin C, a PKC inhibitor. Dopamine did not affect the phosp
horylation of Na+,K+-ATPase isoforms at the PKA-dependent phosphorylation s
ite. Phorbol ester treatment did not alter the phosphorylation of alpha 2 o
r alpha 3 isoforms of Na+,K+-ATPase in neostriatal neurons but did increase
the phosphorylation of the al isoform. Thus, in rat neostriatal neurons, t
reatment with either dopamine or PKC activators results in inhibition of th
e activity of specific (alpha 3 and/or alpha 2) isoforms of Na+,K+-ATPase,
but this is not apparently mediated through direct phosphorylation of the e
nzyme. In addition, PKC is unlikely to mediate inhibition of rat Na+,K+-ATP
ase activity by dopamine in neostriatal neurons.