This project delineates biochemical, chemical, and pharmacological properties of sigma receptors and ligands. At high concentrations, (Tris)hydroxymethyl (aminomethane) Hcl (Tris) inhibits binding to sigma receptors in a dose-dependent and competitive manner. This observation suggests that certain pharmacological responses mediated by sigma receptors could be masked by Tris. Brain homogenate binding assays reveal that sigma-1 and sigma-2 receptor subtypes exhibit different ontogenetic patterns. Sigma-1 receptors remain relatively unchanged from prenatal to postnatal ages (-3 to 90 days). Sigma-2 receptor densities are 10-fold higher at 3 days before birth than at day 30 at which time the densities of sigma-2 and sigma-1 receptors are similar. Subcellular distributions of sigma-1 and sigma-2 receptors do not differ. No differences in sigma-1 or sigma-2 receptors are found when comparing genetically dystonic rats with their normal littermates. Solubilized sigma receptors from rat liver can be resolved into two components by charge partition chromatography. Saturation analysis reveals similar affinities for radiolabeled d-N-allylnormetazocine to both components, suggesting that they do not represent sigma-1 and sigma-2 receptors. Further purification of the receptors is underway.