FLUORESCENT PROBES FOR THE D3 DOPAMINE RECEPTOR

FLUORESCENT PROBES SELECTIVE FOR THE NEWLY IDENTIFIED D-3 DOPAMINE RECEPTOR (DA) ARE BEING DEVELOPED. SINCE ITS DISCOVERY, THE D-3 RECEPTOR HAS BEEN RECOGNIZED AS A MEMBER OF THE D-2 LIKE FAMILY OF DA RECEPTORS AND IS CONSIDERED TO BE A POSSIBLE SITE OF ACTION OF ANTIPSYCHOTICS. RECENTLY, 7-HYDROXY-2-(N,N-DIPROPYL) AMINOTETRALIN (7-OH-DPAT) WAS IDENTIFIED AS A POTENT AND SELECTIVE LIGAND FOR D-3 RECEPTORS. FLUORESCENTLY LABELED ANALOGS OF 7-OH-DPAT ARE BEING PREPARED BY FUNCTIONALIZATION OF ONE OF THE PROPYL CHAINS OF 7-OH-DPAT FOLLOWED BY COUPLING WITH FLUORESCENT REAGENTS. THE AFFINITY OF THESE PROBES FOR D-3 RECEPTORS WILL BE DETERMINED IN BINDING ASSAYS USING MEMBRANES FROM CCL 1.3 FIBROBLASTS THAT EXPRESS CLONED D-3 RECEPTORS. SELECTIVITIES OF THE PROBES WILL ALSO BE DETERMINED BY ASSAYING THEIR AFFINITIES FOR D-1 AND D-2 RECEPTORS. THE ABILITIES OF THE MOST PROMISING PROBES TO SELECTIVELY LABEL D-3 RECEPTORS IN THE CCL 1.3 FIBROBLASTS WILL THEN BE ESTABLISHED BY FLUORESCENCE MICROSCOPIC STUDIES. THE FLUORESCENT PROBES ARE EXPECTED TO BE USEFUL TOOLS FOR THE STUDIES OF D-3 DA RECEPTORS INCLUDING THEIR LOCALIZATION AND DISTRIBUTION IN MAMMALIAN BRAIN.