Posted by Shawn. T. on August 25, 2005, at 18:22:25
In reply to Re: Dextromethorphan? Why?, posted by SLS on August 25, 2005, at 17:38:54
>What do sigma receptors do?
Su TP, Hayashi T.
Understanding the molecular mechanism of sigma-1 receptors: towards a hypothesis that sigma-1 receptors are intracellular amplifiers for signal transduction.
Curr Med Chem. 2003 Oct;10(20):2073-80.
Although sigma receptors were discovered in 1982, the biochemical and physiological roles of sigma receptors have just begun to unveil. Sigma receptors are non-opioid, non-phencyclidine receptors that contain two subtypes: sigma-1 and sigma-2 receptors. The sigma-1 receptor has been cloned and its sequence does not resemble that of any mammalian protein. Sigma-2 receptors have not been cloned. The focus of this review will be on sigma-1 receptors. Sigma-1 receptors contain 223 amino acids and reside primarily at the endoplasmic reticulum. Sigma-1 receptors exist mainly in the central nervous system, but also in the periphery. Sigma-1 receptor ligands include cocaine, (+)-benzomorphans like (+)-pentazocine and (+)N-allyl-normetazocine (or (+)-SKF-10047), and endogenous neurosteroids like progesterone and pregnenolone sulfate. Many pharmacological and physiological actions have been attributed to sigma-1 receptors. These include the regulation of IP3 receptors and calcium signaling at the endoplasmic reticulum, mobilization of cytoskeletal adaptor proteins, modulation of nerve growth factor-induced neurite sprouting, modulation of neurotransmitter release and neuronal firing, modulation of potassium channels as a regulatory subunit, alteration of psychostimulant-induced gene expression, and blockade of spreading depression. Behaviorally, sigma-1 receptors are involved in learning and memory, psychostimulant-induced sensitization, cocaine-induced conditioned place preference, and pain perception. Notably, in almost all the aforementioned biochemical and behavioral tests, sigma-1 agonists, while having no effects by themselves, caused the amplification of signal transductions incurred upon the stimulation of the glutamatergic, dopaminergic, IP3-related metabotropic, or nerve growth factor-related systems. Thus, it is hypothesized that sigma-1 receptors, at least in part, are intracellular amplifiers creating a supersensitized state for signal transduction in the biological system.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12871086
poster:Shawn. T.
thread:546405
URL: http://www.dr-bob.org/babble/20050821/msgs/546648.html