Lack of G protein-coupled sigma receptors in rat brain membranes: receptor-mediated high-affinity GTPase activity and [³⁵S]GTPγS binding studies

Summary.

Although sigma (σ) receptors have been identified as an independent receptor family distinct from opioid and phencyclidine receptors, the physiological roles of these receptors are largely unknown. It is controversial whether there exist metabotropic σ receptors that are coupled with heterotrimeric G proteins. In the present study, the stimulatory effects of σ ligands on high-affinity GTPase activity and [³⁵S]GTPγS binding were determined in the membranes prepared from rat cerebral cortex, hippocampus, and striatum. In either G protein activation assay, none of the σ ligands examined had stimulatory effect in any brain regions, except for unambiguous concentration-dependent increase in [³⁵S]GTPγS binding by (+)-3-(3-hydroxyphenyl)-N-(1-propyl) piperidine [(+)-3-PPP] in striatal membranes. However, the competition study clearly showed this response was mediated through dopamine D₂-like receptors, but not σ receptors. It is concluded that σ receptors are not coupled to heterotrimeric G proteins, at least those of G_i/o type.