Abbreviations used : CGS 21680, 2-[p-(2-carbonylethyl)phenethyl-amino]-5′-N-ethylcarboxamidoadenosine ; CREB, cyclic AMP regulatory element binding protein ; DARPP-32, dopamine- and cyclic AMP-regulated phosphoprotein of Mr 32,000 ; I-1, inhibitor-1 ; IEG, immediate early gene ; KO, knockout ; PP-1, protein phosphatase-1 ; [3H]SCH 23390, 7-chloro-2,3,4,5-tetrahydro-3-[3H]methyl-5-phenyl-1H-3-benzazepine-7-ol ; [3H]SCH 58261, 5-[3H]amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine ; SKF 82958, 6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide ; SSC, standard sodium citrate.
Dopamine D1 Receptor-Induced Gene Transcription Is Modulated by DARPP-32
Article first published online: 25 DEC 2001
Journal of Neurochemistry
Volume 75, Issue 1, pages 248–257, July 2000
How to Cite
Svenningsson, P., Fienberg, A. A., Allen, P. B., Moine, C. L., Lindskog, M., Fisone, G., Greengard, P. and Fredholm, B. B. (2000), Dopamine D1 Receptor-Induced Gene Transcription Is Modulated by DARPP-32. Journal of Neurochemistry, 75: 248–257. doi: 10.1046/j.1471-4159.2000.0750248.x
- Issue published online: 25 DEC 2001
- Article first published online: 25 DEC 2001
- Dopamine- and cyclic AMP-regulated phos;
- Dopamine receptors;
- Immediate early genes;
- In situ hybridization
Abstract : The role of the dopamine- and cyclic AMP-regulated phosphoprotein of Mr 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 D1 and D2 receptors and adenosine A2A 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 D1 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 D2 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.