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Encephale. 1993 May-Jun;19(3):211-4.

[Regulation of the dopamine D2 receptor gene and the early genes in the CNS by neuroleptics].

[Article in French]

Author information

  • 1L.N.M.I.C. (U.P.R. 416 C.N.R.S.), Centre de Neurochimie, Strasbourg.

Abstract

The interaction of a ligand with its cognate receptor not only activates signal transduction pathways but also determines adaptive responses affecting key elements in these pathways, in particular the cell surface receptor. Such is the case for G protein-linked receptors, the expression and functional status of which are highly regulated. The regulatory mechanisms involved can be divided according to two distinct time frames, acute and chronic. In the short-term, posttranslational mechanisms alter the functional status of the elements without changing steady-state levels or gene expression. Protein phosphorylation plays a prominent role in these acute adaptive responses. Thus agonists promote phosphorylation and the desensitization of several G protein-linked receptors. And we have shown in the case of the dopamine D2 receptor that protein kinase C modulates receptor coupling to its G-protein. Longer-term regulation involves transcriptional (gene expression), posttranslational (mRNA stability), and posttranslational (protein phosphorylation) regulation of the turnover of the elements in the information transduction pathway. In the case of G protein-linked receptors, long-term regulation is often reflected in changes in steady-state levels of mRNA (which can be quantified by techniques such as northern blot analysis, solution hybridization or in-situ hybridization). For dopamine D2 receptors, prolonged administration of neuroleptic drugs induces an up-regulation of receptor mRNA in various brain regions, probably through an increase in gene transcription. Receptor-transduced extracellular stimuli are converted into long-term changes in gene expression through specific nuclear transcription factors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID:
8275905
[PubMed - indexed for MEDLINE]
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