The present address of Dr. O. Valdenaire is Pharma Division, Preclinical Research, F. Hoffmann-La Roche, Ltd., Basel, Switzerland.
Retinoic Acid Regulates the Developmental Expression of Dopamine D2 Receptor in Rat Striatal Primary Cultures
Article first published online: 13 NOV 2002
Journal of Neurochemistry
Volume 71, Issue 3, pages 929–936, September 1998
How to Cite
Valdenaire, O., Maus-Moatti, M., Vincent, J.-D., Mallet, J. and Vernier, P. (1998), Retinoic Acid Regulates the Developmental Expression of Dopamine D2 Receptor in Rat Striatal Primary Cultures. Journal of Neurochemistry, 71: 929–936. doi: 10.1046/j.1471-4159.1998.71030929.x
- Issue published online: 13 NOV 2002
- Article first published online: 13 NOV 2002
- Received January 5, 1998; final revised manuscript received March 27, 1998; accepted April 3, 1998.
- Steroid hormones;
- Thyroid hormone;
- Vitamin D3;
- Retinoic acid-responsive element;
- Gene transcription
Abstract: The time course of D2 receptor expression assessed by the levels of the corresponding binding sites and mRNA was studied in rat striatum during ontogenesis and in primary cultures of cells taken at embryonic day (E) 17 and postnatal day (P) 4. In the two experimental situations, the amount of D2 receptor mRNA and number of binding sites increased regularly from E16 to P15, indicating that expression of D2 receptors in striatal neurons occurs independently from a dopaminergic input. Incubation of striatal primary cultures with 10−5M retinoic acid significantly increased the level of D2 receptor mRNA, whereas thyroid hormone, vitamin D3, and steroid hormones (estradiol, testosterone, and corticosterone) had no effect. The transcriptional activity of the rat D2 receptor gene promoter region, which bears a retinoic acid-responsive element, was increased by retinoic acid in transfected C6 glioma cells but not in transfected MMQ prolactin cells. Thyroid hormone and vitamin D3 were not effective in either cell line. Finally, mutations of the putative retinoic acid-responsive element inhibited the transcriptional effect of retinoic acid. These results suggest that retinoic acid is a key factor in regulation of the embryonic onset of the dopaminergic D2 receptor.