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Regulation of Na + , K + ‐ATPase Isoforms in Rat Neostriatum by Dopamine and Protein Kinase C
Author(s) -
Nishi Akinori,
Fisone Gilberto,
Snyder Gretchen L.,
Dulubova Irina,
Aperia Anita,
Nairn Angus C.,
Greengard Paul
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0731492.x
Subject(s) - protein kinase c , dopamine , gene isoform , phosphorylation , protein kinase a , activator (genetics) , biology , dopamine receptor d1 , medicine , dopamine receptor , chemistry , endocrinology , biochemistry , receptor , gene
: Our previous studies showed that dopamine inhibits Na + , K + ‐ATPase activity in acutely dissociated neurons from striatum. In the present study, we have found that in this preparation, dopamine inhibited significantly (by ~25%) the activity of the α3 and/or α2 isoforms, but not the α1 isoform, of Na + , K + ‐ATPase. Dopamine, via D1 receptors, activates cyclic AMP‐dependent protein kinase (PKA) in striatal neurons. Dopamine is also 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 α3 and/or α2 isoforms (by ~30%) as well as the α1 isoform (by ~15%). However, dopamine‐mediated inhibition of Na + , K + ‐ATPase activity was unaffected by calphostin C, a PKC inhibitor. Dopamine did not affect the phosphorylation of Na + , K + ‐ATPase isoforms at the PKA‐dependent phosphorylation site. Phorbol ester treatment did not alter the phosphorylation of α2 or α3 isoforms of Na + , K + ‐ATPase in neostriatal neurons but did increase the phosphorylation of the α1 isoform. Thus, in rat neostriatal neurons, treatment with either dopamine or PKC activators results in inhibition of the activity of specific (α3 and/or α2) isoforms of Na + , K + ‐ATPase, but this is not apparently mediated through direct phosphorylation of the enzyme. In addition, PKC is unlikely to mediate inhibition of rat Na + , K + ‐ATPase activity by dopamine in neostriatal neurons.