Sigma-1 receptor
| Sigma-1 receptor | ||
|---|---|---|
| Properties of human protein | ||
| Mass / length primary structure | 223 amino acids | |
| Isoforms | 5 | |
| Identifier | ||
| Gene name | OPRS1 | |
| External IDs | ||
| Occurrence | ||
| Homology family | Sigma-1 | |
| Parent taxon | Euteleostomi | |
The Sigma-1 receptor belongs to the family of Sigma receptors and is a transmembrane protein in the endoplasmic reticulum (ER) that is found in many different types of tissue in mammals . It is found above average in the liver , intestines , prostate , placenta , small intestine , heart , retina and pancreas . Several vital functions are known, for example in lipid transport from the ER, in the formation of lipid domains in the cell membrane, in the regulation of other receptors and ion channels , as well as in signal transduction using BDNF , EGF and calcium, and last but not least in cell functions such as sprouting and cell death . It plays a role in learning processes, in memory and in mood swings.
The Sigma-1 receptor was purified from guinea pig liver in 1996 using chromatographic methods and the ligand binding site was identified using the photoaffinity ligand azidopamil . The protein-coding cDNA was cloned and expressed heterologously. The amino acid sequence of the receptor does not show any homology to other mammalian proteins, but astonishingly 30% sequence identity and 69% similarity to the ERG2 gene product of the yeasts. The ERG 2 gene product is a C8-C7 sterol isomerase in the metabolic pathway of ergosterol biosynthesis. Therefore, potent fungicides such as B. fenpropimorph , which inhibits ster isomerase, also high binding strength (dissociation constants in the picomolar range) to the mammalian sigma-1 receptor. Clinically used drugs such as raloxifene or amiodarone bind to the mammalian C 8-C 7 sterol isomerase (Emopamil Binding Protein, EPB) and to the Sigma-1 receptor with high affinity.
Repeated cocaine abuse leads to behavioral changes in mice that can be traced back to increased expression of the sigma-1 receptor in the cerebral cortex , striatum and hippocampus . Anti-apoptotic, neuroprotective effects make the receptor a target in the treatment of depression and neurodegenerative diseases of the retina. The drugs opipramol , dextromethorphan and fluvoxamine have high affinities for receptors of the type, as does the atypical neuroleptic quetiapine .
Initially, the receptor was considered an opioid receptor , since opioids develop their antitussive effect via this receptor, but neither endogenous opioids bind to this receptor, nor can the effect of selective σ1 ligands be blocked by naloxone / naltrexone .
Individual evidence
- ↑ UniProt Q99720
- ↑ M. Hanner, FF Moebius, A. Flandorfer, HG Knaus, J. Striessnig, E. Kempner, H. Glossmann : Purification, molecular cloning, and expression of the mammalian sigma1-binding site . In: Proc. Natl. Acad. Sci. USA band 93 , no. 15 , 1996, pp. 8072-8077 , PMID 8755605 , PMC 38877 (free full text).
- ↑ FF Moebius, J. Striessnig, H. Glos man: The mysteries of sigma receptors: new family members reveal a role in cholesterol synthesis . In: Trends Pharmacol. Sci. tape 18 , no. 3 , 1997, p. 67-70 , PMID 9133773 .
- ↑ C. Laggner, C. Schieferer, B. Fiechtner, G. Poles, RD Hoffmann, H. Glossmann, T. Langer, FF Moebius: Discovery of high-affinity ligands of sigma1 receptor, ERG2, and emopamil binding protein by pharmacophore modeling and virtual screening. In: J Med Chem. 48 (15), Jul 28, 2005, pp. 4754-4764.
- ^ Y. Liu, RR Matsumoto: Alterations in fos-related antigen 2 and sigma1 receptor gene and protein expression are associated with the development of cocaine-induced behavioral sensitization: time course and regional distribution studies . In: J. Pharmacol. Exp. Ther. tape 327 , no. 1 , October 2008, p. 187-195 , doi : 10.1124 / jpet.108.141051 , PMID 18591217 .
- ↑ T. Hayashi, TP Su: An update on the development of drugs for neuropsychiatric disorders: focusing on the sigma 1 receptor ligand . In: Expert Opin. Ther. Targets . tape 12 , no. 1 , January 2008, p. 45-58 , doi : 10.1517 / 14728222.12.1.45 , PMID 18076369 .
- ^ Y. Dun, M. Thangaraju, P. Prasad, V. Ganapathy, SB Smith: Prevention of excitotoxicity in primary retinal ganglion cells by (+) - pentazocine, a sigma receptor-1 specific ligand . In: Invest. Ophthalmol. Vis. Sci. tape 48 , no. 10 , October 2007, p. 4785-4794 , doi : 10.1167 / iovs.07-0343 , PMID 17898305 .
- ^ WR Martin, CG Eades, JA Thompson, RE Huppler, PE Gilbert: The effects of morphine- and nalorphine-like drugs in the nondependent and morphine-dependent chronic spinal dog . In: J. Pharmacol. Exp. Ther. tape 197 , no. 3 , 1976, p. 517-532 , PMID 945347 .