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Phosphorylation of DARPP‐32 Is Regulated by GABA in Rat Striatum and Substantia Nigra
Author(s) -
Snyder Gretchen L.,
Fisone Gilberto,
Greengard Paul
Publication year - 1994
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.1471-4159.1994.63051766.x
Subject(s) - substantia nigra , striatum , neuroscience , chemistry , medium spiny neuron , phosphorylation , dopamine , biology , biochemistry , dopaminergic
In the medium‐sized spiny neurons of the striatonigral pathway, a cascade of events involving the activation of dopamine D 1 receptors, an increase in cyclic AMP, and activation of cyclic AMP‐dependent protein kinase causes the phosphorylation of DARPP‐32 on Thr 34 , converting DARPP‐32 into a powerful inhibitor of protein phosphatase‐1. In the present study, the incubation of striatal or substantia nigra slices with GABA also increased the phosphorylation of DARPP‐32 on Thr 34 . GABA did not significantly increase cyclic AMP levels in slices. The phosphorylation of DARPP‐32 by GABA was blocked in both brain regions by pretreatment of slices with the GABA A receptor antagonist, bicuculline, but not with the GABA B receptor antagonist, phaclofen. Moreover, the threonine phosphorylation of DARPP‐32 produced by maximally effective doses of either forskolin (in striatum) or l ‐3,4‐dihydroxyphenylalanine (in substantia nigra) was increased further by GABA. The data are consistent with a model in which GABA increases the phosphorylation state of DARPP‐32 by inhibiting dephosphorylation of the protein by the calcium/calmodulin‐dependent protein phosphatase, calcineurin.