Regulation of Agonist Interactions with Brain D-1 Dopamine Receptors

Abstract

Extensive characterization of both agonist and antagonist interactions with mammalian D-2 dopamine receptors have been carried out using radioligand binding techniques coupled more recently with computer-assisted data analyses (for review see Creese et al. 1983). However, except for a preliminary study of some novel dopaminergic agonists (Sibley et al., 1982a) no such detailed analyses have been reported describing the interaction of dopaminergic agonists with the D-1 dopamine receptor labeled with [3H]antagonist ligands. Earlier studies indicated that D-1 dopamine receptors in calf and rat striatum can be labeled by the thioxanthene antagonists [3H]flupentixol and [3H]piflutixol (for example Hyttel, 1980). The regional distribution in brain of dopamine-stimulated adenylate cyclase activity and specific, high-affinity [3H]flupentixol binding are similar, and dopaminergic antagonists block both activities with a highly correlated rank-order of potency. Unfortunately [3H]flupentixol is not selective and labels D-2 as well as D-1 dopamine receptors in striatum (Cross and Owen, 1980; Hyttel, 1981; Sibley et al., 1982).