RETINOIC ACID REGULATES THE DEVELOPMENTAL EXPRESSION OF DOPAMINE D-2 RECEPTOR IN RAT STRIATAL PRIMARY CULTURES

The time course of D-2 receptor expression assessed by the levels of t he corresponding binding sites and mRNA was studied in rat striatum du ring ontogenesis and in primary cultures of cells taken at embryonic d ay (E) 17 and postnatal day (P) 4. In the two experimental situations, the amount of D-2 receptor mRNA and number of binding sites increased regularly from El 6 to P15, indicating that expression of D-2 recepto rs in striatal neurons occurs independently from a dopaminergic input, Incubation of striatal primary cultures with 10(-5) M retinoic acid s ignificantly increased the level of D-2 receptor mRNA, whereas thyroid hormone, vitamin D-3, and steroid hormones (estradiol, testosterone, and corticosterone) had no effect. The transcriptional activity of the rat D-2 receptor gene promoter region, which bears a retinoic acid-re sponsive element, was increased by retinoic acid in transfected C6 gli oma cells but not in transfected MMQ prolactin cells. Thyroid hormone and vitamin D-3 were not effective in either cell line. Finally, mutat ions of the putative retinoic acid-responsive element inhibited the tr anscriptional effect of retinoic acid. These results suggest that reti noic acid is a key factor in regulation of the embryonic onset of the dopaminergic D-2 receptor.