The publication detail shows the title, authors (with indicators showing other profiled authors), information on the publishing organization, abstract and a link to the article in PubMed. This abstract is what is used to create the fingerprint of the publication. If any grants are referenced by the publication, they will be listed here as well.
Histone H3 phosphorylation is under the opposite tonic control of dopamine D2 and adenosine A2A receptors in striatopallidal neurons.
Jesus Bertran-Gonzalez; Kerstin Håkansson; Anders Borgkvist; Theano Irinopoulou; Karen Brami-Cherrier; Alessandro Usiello; Paul Greengard; Denis Hervé; Jean-Antoine Girault; Emmanuel Valjent; et al. (Profiled Author: Greengard, Paul)
Inserm, UMR-S 839, Paris, France.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 2009;34(7):1710-20.
The antipsychotic agent haloperidol regulates gene transcription in striatal medium spiny neurons (MSNs) by blocking dopamine D2 receptors (D2Rs). We examined the mechanisms by which haloperidol increases the phosphorylation of histone H3, a key step in the nucleosomal response. Using bacterial artificial chromosome (BAC)-transgenic mice that express EGFP under the control of the promoter of the dopamine D1 receptor (D1R) or the D2R, we found that haloperidol induced a rapid and sustained increase in the phosphorylation of histone H3 in the striatopallidal MSNs of the dorsal striatum, with no change in its acetylation. This effect was mimicked by raclopride, a selective D2R antagonist, and prevented by the blockade of adenosine A2A receptors (A2ARs), or genetic attenuation of the A2AR-associated G protein, Galpha(olf). Mutation of the cAMP-dependent phosphorylation site (Thr34) of the 32-kDa dopamine and cAMP-regulated phosphoprotein (DARPP-32) decreased the haloperidol-induced H3 phosphorylation, supporting the role of cAMP in H3 phosphorylation. Haloperidol also induced extracellular signal-regulated kinase (ERK) phosphorylation in striatopallidal MSNs, but this effect was not implicated in H3 phosphorylation. The levels of mitogen- and stress-activated kinase 1 (MSK1), which has been reported to mediate ERK-induced H3 phosphorylation, were lower in striatopallidal than in striatonigral MSNs. Moreover, haloperidol-induced H3 phosphorylation was unaltered in MSK1-knockout mice. These data indicate that, in striatopallidal MSNs, H3 phosphorylation is controlled by the opposing actions of D2Rs and A2ARs. Thus, blockade of D2Rs promotes histone H3 phosphorylation through the A2AR-mediated activation of Galpha(olf) and inhibition of protein phosphatase-1 (PP-1) through the PKA-dependent phosphorylation of DARPP-32.
2 Originating Grant
1 March 1997 - 29 February 2016
NATIONAL INSTITUTE ON DRUG ABUSE
Total Funding: $ 24,977,507
1 July 1985 - 30 June 2005
NATIONAL INSTITUTE OF MENTAL HEALTH
Total Funding: $ 27,221,874
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