Identification of the Sigma-2 Receptor: Distinct from the Progesterone Receptor Membrane Component 1 (PGRMC1).

Takato Hiranita

doi:10.4172/2329-6488.1000e130

Abstract

σRs are unique intracellular chaperone proteins [8] initially thought to be opioid receptor subtypes [9]. They have been classified into two subtypes based on specific radioligand binding assays using [3H](+)pentazocine for σ1Rs and [3H]1,3-di-o-tolylguanidine ([3H]DTG, in the presence of dextrallorphan to mask the σ1R) for σ2Rs in rat liver and kidney membranes [10]. Currently, the more selective σ1R ligand (+)-pentazocine has replaced dextrallorphan to mask the σ1R [7,11-14]. The σ1R has already been cloned as a 25-29 kDa chaperone protein composed of 223 amino acids [4,8,15]. It is widely distributed throughout the body [16-20]. Upon binding with agonists or under cellular stress, σ1Rs translocate from their primary endoplasmic reticulum (ER) location to different subcellular compartments where they can regulate ion channels and G-protein-coupled-receptor (GPCR) signaling [8,21-24]. In vivo functional studies on σ1Rs suggest that they play a substantial role in various cellular functions. Drugs acting at this receptor have been studied for their potential therapeutic effects in cancer, human immunodeficiency virus (HIV) infection, various psychiatric disorders, and substance abuse [1,25].

Highlights

The sigma receptor subtypes, σ1 and σ2, have been mischaracterized [1,2]
A recent study suggested that the σ2R is the progesterone receptor membrane component 1 (PGRMC1) in rat livers
ΣRs are unique intracellular chaperone proteins [8] initially thought to be opioid receptor subtypes [9]. They have been classified into two subtypes based on specific radioligand binding assays using [3H](+)-pentazocine for σ1Rs and [3H]1,3-di-o-tolylguanidine ([3H]DTG, in the presence of dextrallorphan to mask the σ1R) for σ2Rs in rat liver and kidney membranes [10]

Summary

Introduction

A recent study suggested that the σ2R is the progesterone receptor membrane component 1 (PGRMC1) in rat livers. They have been classified into two subtypes based on specific radioligand binding assays using [3H](+)-pentazocine for σ1Rs and [3H]1,3-di-o-tolylguanidine ([3H]DTG, in the presence of dextrallorphan to mask the σ1R) for σ2Rs in rat liver and kidney membranes [10]. Upon binding with agonists or under cellular stress, σ1Rs translocate from their primary endoplasmic reticulum (ER) location to different subcellular compartments where they can regulate ion channels and G-protein-coupled-receptor (GPCR) signaling [8,21,22,23,24].

Results

Conclusion