Regulation of Na+,K+-ATPase isoforms in rat neostriatum by dopamine and protein kinase C

Citation
A. Nishi et al., Regulation of Na+,K+-ATPase isoforms in rat neostriatum by dopamine and protein kinase C, J NEUROCHEM, 73(4), 1999, pp. 1492-1501
Citations number
46
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROCHEMISTRY
ISSN journal
00223042 → ACNP
Volume
73
Issue
4
Year of publication
1999
Pages
1492 - 1501
Database
ISI
SICI code
0022-3042(199910)73:4<1492:RONIIR>2.0.ZU;2-M
Abstract
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.