Dopamine D2 receptor dimer formation -: Evidence from ligand binding

We have examined the binding of two radioligands ([H-3]spiperone and [SH]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 [H-3]raclopride labeled about half the number of sites labeled by [H-3]spiperone. In competition experiments in the absence of sodium ions, however, raclopride was able to inhibit [H-3]spiperone binding fully. In saturation analyses with [H-3]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.