Evidence that the sigma(1) receptor is not directly coupled to G proteins
Related Experiment Video
Updated: Oct 10, 2026

Measuring G-protein-coupled Receptor Signaling via Radio-labeled GTP Binding
Published on: June 9, 2017
1Neuroscience Program, The George Washington University Medical Center, Washington, DC 20037, USA.
Abstract:
Sigma (sigma) receptors have been implicated in psychosis, cognition, neuroprotection, and locomotion in the central nervous system. The signal transduction mechanisms for sigma receptors have not been fully elucidated. In this study, we examined the possible coupling between sigma(1) receptors and heterotrimeric guanine nucleotide-binding proteins (G proteins) in rodent brain. In sigma(1) receptor-rich cerebellar membrane preparations, the competitive binding curves of two sigma(1) agonists, (+)pentazocine and 1S,2R-(-)-cis-N-[2-(3, 4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)cyclohexylamine (BD737), were unaffected by the addition of 10 microM guanosine-5'-O-(gamma-thio)-triphosphate (GTPgammaS). Neither (+)pentazocine (1-100 microM) nor BD737 (0.01-10 microM) stimulated GTPase activities significantly above basal levels in agonist-stimulated GTPase activity assays in cerebellar membranes. Furthermore, when using the method of agonist-stimulated [35S]GTPgammaS binding as assessed by autoradiography, we did not observe significant stimulation of [35S]GTPgammaS binding in rat brain sections by either (+)pentazocine or BD737. The above results demonstrate that the sigma(1) receptor is not likely be directly coupled to G proteins.
More Related Videos
09:40Imaging G-protein Coupled Receptor (GPCR)-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum
Published on: September 20, 2011
07:41A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
Published on: February 20, 2018
Related Concept Videos
G Protein-coupled Receptors
G-protein Coupled Receptors
Activation and Inactivation of G Proteins
GPCR Desensitization
G Protein-coupled Receptors
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs Regulate Adenylyl Cylase Activity
Two...