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Dopamine D 1 Receptor‐Induced Gene Transcription Is Modulated by DARPP‐32
Author(s) -
Svenningsson Per,
Fienberg Allen A.,
Allen Patrick B.,
Moine Catherine Le,
Lindskog Maria,
Fisone Gilberto,
Greengard Paul,
Fredholm Bertil B.
Publication year - 2000
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.1471-4159.2000.0750248.x
Subject(s) - dopaminergic , medicine , globus pallidus , dopamine , dopamine receptor d2 , endocrinology , agonist , striatum , dopamine receptor , dopamine receptor d1 , receptor , biology , basal ganglia , chemistry , central nervous system
: The role of the dopamine‐ and cyclic AMP‐regulated phosphoprotein of M r 32,000 (DARPP‐32) in dopaminergic regulation of gene transcription in striatum and globus pallidus was examined. Mice with targeted disruption of the gene encoding DARPP‐32, its homologue, inhibitor‐1, or both, were used. Pharmacological characterization showed that mutant mice had normal basal levels of dopamine D 1 and D 2 receptors and adenosine A 2A receptors. Basal expression levels of the striatonigral‐specific neuropeptides substance P and prodynorphin and the immediate early genes c‐ fos and NGFI‐A were also unaltered in mutant mice. A full D 1 receptor agonist, SKF 82958, up‐regulated the expression of these neuropeptides and immediate early genes significantly more in wild‐type mice than in mice lacking DARPP‐32. Moreover, the additive stimulation of SKF 82958 and quinelorane, a D 2 receptor agonist, on c‐ fos mRNA in globus pallidus was significantly decreased in DARPP‐32 and DARPP‐32/I‐1 knockout mice. No changes in dopamine receptor‐induced gene expression were found in I‐1 knockout mice. These results demonstrate an important involvement of DARPP‐32 in dopamine receptor‐mediated regulation of gene expression both in striatal neurons, which are enriched in DARPP‐32, and in pallidal neurons, which do not contain DARPP‐32.