Dopamine D2 receptor dimers in human and rat brain

Abstract

In order to determine whether dimers of dopamine D2 receptors can occur in mammalian brain, rat and human brain striatal membranes were photolabelled with two radioactive photoaffinity compounds selective for dopamine D2 receptors, [125I]azidophenethylspiperone and [125I]-4-azido-5-iodonemonapride. It was found that [125I]azidophenethylspiperone only labelled the D2 monomer, while [125I]-4-azido-5-iodonemonapride labelled both D2 monomers and dimers, despite the fact that very high concentrations (6 nM) of both radiocompounds were used. In addition, human cloned D2 receptors were probed with a D2-specific antibody, revealing multiple bands indicating the existence of trimers, tetramers and pentamers of D2 receptors. The different D2-binding patterns of the spiperone and benzamide congeners may explain the different densities of dopamine D2 receptors found with these two radioligands in human brain positron tomography in health and disease.