General aspects of D1 receptors

In the presence of a D2 antagonist, the binding of [3H]dopamine to rat brain sections is very selective for dopamine D1 sites, and is entirely displaced by low concentrations of the prototypic D1 antagonist Sch 23390 (Herve et al. 1992). However, the D1 receptors linked to adenylate cyclase may constitute a subset of the binding sites for [3H]Sch 23390 (Andersen & Braestrup 1986). In the absence of sodium ion, two affinity states of dopamine D1 receptors for dopamine can be distinguished. The high-affinity state of the receptor, which is sensitive to the presence of GTP, seems to constitute about one half of the total binding in membranes prepared from bovine caudate (Seeman et al. 1985). Likewise, increasing concentrations of a D1 agonist displace [3H]Sch 23390 from D1 receptors in human caudate in a biphasic manner, revealing approximately equal proportions of D1Low and D1High states of the receptor. In contrast, others report the fraction of dopamine D1 receptors in rat cryostat sections in a high-affinity state for dopamine to be only 20%, versus 77% for D2 receptors (Richfield, Penney, & Young 1989).

The regulation of dopamine D1 receptor expression in living brain is poorly understood. Steroid hormones play a role, since the striatal binding of [3H]Sch 23390 in female rat decreased following ovariectomy, and varied across the estrus cycle (Levesque, Gagnon, & Di Paolo 1989).