Abstract

This project delineates biochemical, chemical, and pharmacological properties of sigma receptors and ligands. Sigma ligands are examined for a modulation of the NMDA receptor complex-mediated learning processes. Learning capacities are evaluated using the spontaneous alternation in a Y-maze test for spatial working memory, and the step-down passive avoidance and the elevated plus-maze test for long-term memory. PRE-084, a selective sigma ligand discovered at this laboratory, attenuate MK-801-induced impairment of memory processes in all three tests. These effects of PRE-084 are antagonized by a sigma receptor antagonist BMY-14802. Solubilized sigma receptors are partially purified using anion-exchange and hydrophobic interaction chromatographies. Throughout the chromatographic procedures, a chromophore with a strong absorbance at 415 nm co-migrates with sigma receptors. The result suggests that sigma receptors may have a close relationship with a chromophore. Further purification of the receptors is underway.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Intramural Research (Z01)
Project #
1Z01DA000206-09
Application #
3752858
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

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

  Publications

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
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
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
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
Takebayashi, M; Hayashi, T; Su, T-P (2004) A perspective on the new mechanism of antidepressants: neuritogenesis through sigma-1 receptors. Pharmacopsychiatry 37 Suppl 3:S208-13
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

Showing the most recent 10 out of 21 publications