Mol 12443 1

1 Investigation of cooperativity in the binding of ligands to the D 2 dopamine receptor. Abstract The D 2 dopamine receptor exists as dimers or as higher order oligomers, based on data from physical experiments. In this study we have sought evidence that this oligomerisation leads to cooperativity by examining the binding of three radioligands ([ 3 H]nemonapride, [ 3 H]raclopride, [ 3 H]spiperone) to D 2 dopamine receptors expressed in membranes of Sf 9 cells. In saturation binding experiments the three radioligands exhibited different B max values and the B max values could be altered by addition of sodium ions to assays. Despite labelling 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 [ 3 H]nemonapride or [ 3 H]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 behaviour 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 behaviour of this receptor. This article has not been copyedited and formatted. The final version may differ from this version.