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The sigma-1 receptor (σ1R), one of two sigma receptor subtypes, is a chaperone protein at the endoplasmic reticulum (ER) that modulates calcium signaling through the IP3 receptor.[5] In humans, the σ1 receptor is encoded by the SIGMAR1 gene.[6][7]
The σ1 receptor is a transmembrane protein expressed in many different tissue types. It is particularly concentrated in certain regions of the central nervous system.[8] It has been implicated in several phenomena, including cardiovascular function, schizophrenia, clinical depression, the effects of cocaine abuse, bipolar disorder, and cancer.[9][10] Much is known about the binding affinity of hundreds of synthetic compounds to the σ1 receptor.
An endogenous ligand for the σ1 receptor has yet to be conclusively identified, but tryptaminergic trace amines and neuroactive steroids have been found to activate the receptor.[11] Especially progesterone, but also testosterone, pregnenolone sulfate, N,N-Dimethyltryptamine (DMT) and dehydroepiandrosterone sulfate (DHEA-S) bind to the σ1 receptor.[12]
- ^ a b c GRCh38: Ensembl release 89: ENSG00000147955 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000036078 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Hayashi T, Su TP (November 2007). "Sigma-1 receptor chaperones at the ER-mitochondrion interface regulate Ca(2+) signaling and cell survival". Cell. 131 (3): 596–610. doi:10.1016/j.cell.2007.08.036. PMID 17981125. S2CID 18885068.
- ^ Kekuda R, Prasad PD, Fei YJ, Leibach FH, Ganapathy V (December 1996). "Cloning and functional expression of the human type 1 sigma receptor (hSigmaR1)". Biochemical and Biophysical Research Communications. 229 (2): 553–558. doi:10.1006/bbrc.1996.1842. PMID 8954936.
- ^ Prasad PD, Li HW, Fei YJ, Ganapathy ME, Fujita T, Plumley LH, et al. (February 1998). "Exon-intron structure, analysis of promoter region, and chromosomal localization of the human type 1 sigma receptor gene". Journal of Neurochemistry. 70 (2): 443–451. doi:10.1046/j.1471-4159.1998.70020443.x. PMID 9453537. S2CID 22305479.
- ^ Weissman AD, Su TP, Hedreen JC, London ED (October 1988). "Sigma receptors in post-mortem human brains". The Journal of Pharmacology and Experimental Therapeutics. 247 (1): 29–33. PMID 2845055.
- ^ Guitart X, Codony X, Monroy X (July 2004). "Sigma receptors: biology and therapeutic potential". Psychopharmacology. 174 (3): 301–319. doi:10.1007/s00213-004-1920-9. PMID 15197533. S2CID 23606712.
- ^ Zhang H, Cuevas J (June 2005). "sigma Receptor activation blocks potassium channels and depresses neuroexcitability in rat intracardiac neurons". The Journal of Pharmacology and Experimental Therapeutics. 313 (3): 1387–1396. doi:10.1124/jpet.105.084152. PMID 15764734. S2CID 9704436.
- ^ Fontanilla D, Johannessen M, Hajipour AR, Cozzi NV, Jackson MB, Ruoho AE (February 2009). "The hallucinogen N,N-dimethyltryptamine (DMT) is an endogenous sigma-1 receptor regulator". Science. 323 (5916): 934–937. Bibcode:2009Sci...323..934F. doi:10.1126/science.1166127. PMC 2947205. PMID 19213917.
- ^ Hayashi T, Su TP (2004). "Sigma-1 receptor ligands: potential in the treatment of neuropsychiatric disorders". CNS Drugs. 18 (5): 269–284. doi:10.2165/00023210-200418050-00001. PMID 15089113. S2CID 72726251.
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