Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Intramural Research (Z01)
Project #
1Z01DA000206-11
Application #
2571621
Study Section
Special Emphasis Panel ( NS)
Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
1996
Total Cost
Indirect Cost

  Institution

Name
National Institute on Drug Abuse
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Cormaci, Gianfrancesco; Mori, Tomohisa; Hayashi, Teruo et al. (2007) Protein kinase A activation down-regulates, whereas extracellular signal-regulated kinase activation up-regulates sigma-1 receptors in B-104 cells: Implication for neuroplasticity. J Pharmacol Exp Ther 320:202-10
Hayashi, Teruo; Su, Tsung-Ping (2007) Sigma-1 receptor chaperones at the ER-mitochondrion interface regulate Ca(2+) signaling and cell survival. Cell 131:596-610
Tsai, Shang-Yi; Hayashi, Teruo; Su, Tsung-Ping (2005) Picomolar concentrations of hibernation induction delta opioid peptide [D-Ala2,D-Leu5]enkephalin increase the nerve growth factor in NG-108 cells. Synapse 57:179-81
Hayashi, Teruo; Su, Tsung-Ping (2005) The potential role of sigma-1 receptors in lipid transport and lipid raft reconstitution in the brain: implication for drug abuse. Life Sci 77:1612-24
Marrazzo, Agostino; Caraci, Filippo; Salinaro, Elisa Trovato et al. (2005) Neuroprotective effects of sigma-1 receptor agonists against beta-amyloid-induced toxicity. Neuroreport 16:1223-6
Hayashi, Teruo; Su, Tsung-Ping (2004) Sigma-1 receptor ligands: potential in the treatment of neuropsychiatric disorders. CNS Drugs 18:269-84
Peeters, Magali; Romieu, Pascal; Maurice, Tangui et al. (2004) Involvement of the sigma 1 receptor in the modulation of dopaminergic transmission by amantadine. Eur J Neurosci 19:2212-20
Takebayashi, Minoru; Hayashi, Teruo; Su, Tsung-Ping (2004) Sigma-1 receptors potentiate epidermal growth factor signaling towards neuritogenesis in PC12 cells: potential relation to lipid raft reconstitution. Synapse 53:90-103
Hayashi, Teruo; Su, Tsung-Ping (2004) Sigma-1 receptors at galactosylceramide-enriched lipid microdomains regulate oligodendrocyte differentiation. Proc Natl Acad Sci U S A 101:14949-54
Stefanski, Roman; Justinova, Zuzana; Hayashi, Teruo et al. (2004) Sigma1 receptor upregulation after chronic methamphetamine self-administration in rats: a study with yoked controls. Psychopharmacology (Berl) 175:68-75

Showing the most recent 10 out of 21 publications