RT Journal Article SR Electronic T1 Investigation of Cooperativity in the Binding of Ligands to the D2 Dopamine Receptor JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 226 OP 235 DO 10.1124/mol.105.012443 VO 69 IS 1 A1 Vivo, Meritxell A1 Lin, Hong A1 Strange, Philip G. YR 2006 UL http://molpharm.aspetjournals.org/content/69/1/226.abstract AB The D2 dopamine receptor exists as dimers or as higher-order oligomers, as determined from data from physical experiments. In this study, we sought evidence that this oligomerization leads to cooperativity by examining the binding of three radioligands ([3H]nemonapride, [3H]raclopride, and [3H]spiperone) to D2 dopamine receptors expressed in membranes of Sf9 cells. In saturation binding experiments, the three radioligands exhibited different Bmax values, and the Bmax values could be altered by the addition of sodium ions to assays. Despite labeling different numbers of sites, the different ligands were able to achieve full inhibition in competition experiments. Some ligand pairs also exhibited complex inhibition curves in these experiments. In radioligand dissociation experiments, the rate of dissociation of [3H]nemonapride or [3H]spiperone depended on the sodium ion concentration but was independent of the competing ligand. Although some of the data in this study are consistent with the behavior of a cooperative oligomeric receptor, not all of the data are in agreement with this model. It may, therefore, be necessary to consider more complex models for the behavior of this receptor.