Cross-talk between an activator of nuclear receptors-mediated transcription and the D sub(1) dopamine receptor signaling pathway

• Published in: Pharmacology, biochemistry and behavior biochemistry and behavior, 2005-03, Vol.80 (3), p.379-385
• Main Authors: Schmidt, A, Vogel, R, Rutledge, S J, Opas, EE, Rodan, G A, Friedman, E
• Format: Article
• Language: English
• Subjects: Mouse mammary tumor virus
• ISSN: 0091-3057
• DOI: 10.1016/j.pbb.2004.11.013

Nuclear receptors are transcription factors that usually interact, in a ligand-dependent manner, with specific DNA sequences located within promoters of target genes. The nuclear receptors can also be controlled in a ligand- independent manner via the action of membrane receptors and cellular signaling pathways. 5-Tetradecyloxy-2-furancarboxylic acid (TOFA) was shown to stimulate transcription from the MMTV promoter via chimeric receptors that consist of the DNA binding domain of GR and the ligand binding regions of the PPAR beta or LXR beta nuclear receptors (GR/PPAR beta and GR/LXR beta ). TOFA and hydroxycholesterols also modulate transcription from NF- Kappa B-and AP-1- controlled reporter genes and induce neurite differentiation in PC12 cells. In CV-1 cells that express D sub(1) dopamine receptors, D sub(1) dopamine receptor stimulation was found to inhibit TOFA-stimulated transcription from the MMTV promoter that is under the control of chimeric GR/PPAR beta and GR/LXR beta receptors. Treatment with the D sub(1) dopamine receptor antagonist, SCH23390, prevented dopamine-mediated suppression of transcription, and by itself increased transcription controlled by GR/LXR beta . Furthermore, combined treatment of CV-1 cells with TOFA and SCH23390 increased transcription controlled by the GR/LXR beta chimeric receptor synergistically. The significance of this in vitro synergy was demonstrated in vivo, by the observation that SCH23390 (but not haloperidol)-mediated catalepsy in rats was potentiated by TOFA, thus showing that an agent that mimics the in vitro activities of compounds that activate members of the LXR and PPAR receptor families can influence D1 dopamine receptor elicited responses.