Purification, molecular cloning, and expression of the mammalian sigma1-binding site.

Abstract

Sigma-ligands comprise several chemically unrelated drugs such as haloperidol, pentazocine, and ditolylguanidine, which bind to a family of low molecular mass proteins in the endoplasmic reticulum.

Novel sigma (σ) receptor agonists produce antidepressant-like effects in mice

“…In the1980s, binding studies by Tsung-Ping Su indicated that σ receptors were new and previously uncharacterized receptors (Su, 1981;Su, 1982). When the receptor was cloned in the 1990s, the results confirmed that its sequence differed from all other known proteins (Hanner et al, 1996). The endogenous ligand for σ receptors has yet to be conclusively determined, although the identity of the receptor protein is now well established.…”

“…The σ-1 subtype has been cloned from various species, such as rat, mouse, and human (Hanner et al, 1996;Seth et al, 1997;Pan et al, 1998;Seth et al, 1998;Mei and Pasternak, 2001). It is a 233 amino acid protein with two putative transmembrane spanning regions (Jbilo et al, 1997;Aydar et al, 2002).…”

Involvement of the Sigma1 Receptor in Cocaine-induced Conditioned Place Preference Possible Dependence on Dopamine Uptake Blockade

“…An alternative therapeutic approach to treating cocaine addiction, therefore, would be to target the sigma 1 receptor, which has recently been demonstrated to be involved in cocaine's rewarding effects measured using a conditioned place preference (CPP) paradigm in mice (Romieu et al 2000). The sigma 1 receptor, localized intracellularly within the neurons, is a 223 amino acid protein, cloned in several animal species and humans (Hanner et al 1996;Kekuda et al 1996;Seth et al 1997Seth et al , 1998Pan et al 1998). The receptor appeared devoid of analogy with any other known mammalian protein and its endogenous ligand has still to be established, but its regional and subcellular distributions have recently been determined by immunohistochemical labeling in rodents Phan et al 2000).…”

Synthesis, Biological Evaluation, and Three-Dimensional in Silico Pharmacophore Model for σ1 Receptor Ligands Based on a Series of Substituted Benzo[d]oxazol-2(3H)-one Derivatives

“…11 The σ 1 receptor subtype has been purified and cloned from several animal species and man. 12,13 Its primary sequence is now available and shows remarkable homology with sterol C8-C7 isomerase from fungi. The σ 1 receptors exert a modulatory role on neurotransmitter systems such as dopaminergic, serotoninergic, and muscarinic systems 5,14,15 and on the NMDA-stimulated neurotransmitters' release.…”