A D1/D2 chimeric dopamine receptor mediates a D1 response to a D2-selective agonist.

D1 and D2 dopamine receptors are G-protein coupled receptors and have seven transmembrane spanning regions (TM) typical of this receptor superfamily. Although dopamine binds equally to D1 and D2 receptors, many compounds are highly selective. To probe the receptors for regions that determine subtype specificity, plasmid constructs coding for the D1 or a D1/D2 chimeric receptor were made and transfected into cells to study the binding and agonist properties of non-selective or subtype-selective compounds. The results suggest that the D2-selective agonist, quinpirole, gains much of its selectivity by binding to within TM VI and VII of the D2 receptor.