Dopamine D2 receptor dimer formation: evidence from ligand binding.

We have examined the binding of two radioligands ([(3)H]spiperone and [(3)H]raclopride) to D(2) dopamine receptors expressed in Chinese hamster ovary cells. In saturation binding experiments in the presence of sodium ions, both radioligands labeled a similar number of sites, whereas in the absence of sodium ions [(3)H]raclopride labeled about half the number of sites labeled by [(3)H]spiperone. In competition experiments in the absence of sodium ions, however, raclopride was able to inhibit [(3)H]spiperone binding fully. In saturation analyses with [(3)H]spiperone in the absence of sodium ions raclopride exerted noncompetitive effects, decreasing the number of sites labeled by the radioligand. These data are interpreted in terms of a model where the receptor exists as a dimer, and in the absence of sodium ions, raclopride exerts negative cooperativity across the dimer both for its own binding and the binding of spiperone. A model of the receptor has been produced that provides a good description of the experimental phenomena described here.