BIOLOGICAL AND BIOCHEMICAL CHARACTERIZATION OF SIGMA RECEPTORS

该项目描述的生化和药理学性质

This project delineates biochemical and pharmacological properties of sigma receptors and ligands. Using an affinity chromatography which purified sigma receptors by 2,000 folds in one step, a unique protein, with a pharmacological profile consistent with the original opioid/sigma receptor hypothesized by Martin etal., was discovered. This protein is sensitive to naloxone and the psychotomimetic benzomorphans such as cyclazocine and pentazocine. In a biochemical study, sigma receptors were found to reside in close proximity to IP3 receptors which mobilize extracellular and intracellular calcium. Behavioral, PRE-084 - a selective sigma ligand identified by this lab - was found to improve impairment of learning and memory in both the nimodipine-treated animals and in the genetically senescence-accelerated mice (SAM). Additionally, an agonist at the NMDA receptor-associated glycine site was found to reverse the 825-35 amyloid-induced amnesia. PRE-084 is currently being investigated to see if it may reverse the amnesia induced by 825-35 amyloid.