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Sigma receptor

From Wikipedia, the free encyclopedia
Class of cell surface receptors

This articlemay be too technical for most readers to understand. Pleasehelp improve it tomake it understandable to non-experts, without removing the technical details.(August 2020) (Learn how and when to remove this message)
Protein family
ERG2/Sigma-1 receptor
Identifiers
SymbolERG2_Sigma1R
PfamPF04622
InterProIPR006716
TCDB8.A.63
OPM superfamily446
OPM protein5hk1
Membranome1025
Available protein structures:
Pfam  structures /ECOD  
PDBRCSB PDB;PDBe;PDBj
PDBsumstructure summary
Protein family
Sigma intracellular receptor 2
Identifiers
SymbolSigma2
InterProIPR016964

Sigma receptors (σ-receptors) areproteinreceptors that bindligands such as4-PPBP (4-phenyl-1-(4-phenylbutyl) piperidine),[1]SA 4503 (cutamesine),ditolylguanidine,dimethyltryptamine,[2] andsiramesine.[3] There are two subtypes,sigma-1 receptors (σ1) andsigma-2 receptors (σ2), which are classified as sigma receptors for their pharmacological similarities, even though they are evolutionarily unrelated.

The fungal protein ERG2, a C-8 sterol isomerase, falls into the sameprotein family as sigma-1. Both localize to theER membrane, although sigma-1 is also reported to be a cell surface receptor. Sigma-2 is an EXPERA domain protein[4] with a mostly intracellular (ER membrane) localization.[5]

Classification

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Because the σ-receptor was originally discovered to be agonized bybenzomorphanopioids and antagonized bynaltrexone, σ-receptors were originally believed to be a type of opioid receptor.[6] When the σ1 receptor was isolated and cloned, it was found to have no structural similarity to the opioid receptors, but rather showed similarity to fungal proteins involved in sterol synthesis.[7] At this point, they were designated as a separate class of proteins.

Function

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The function of these receptors is poorly understood.[8] Drugs known to be σ-agonists includecocaine,morphine/diacetylmorphine,opipramol,PCP,fluvoxamine,methamphetamine,dextromethorphan, andberberine.[citation needed] However, the exact role of σ-receptors is difficult to establish as many σ-agonists also bind to other targets such as theκ-opioid receptor and theNMDA glutamate receptor. In animal experiments, σ-antagonists such asrimcazole were able to block convulsions from cocaine overdose. σ-antagonists are also under investigation for use asantipsychotic medications.

The abundant neurosteroid steroid hormoneDHEA is an agonist at sigma receptors and along withpregnenolone could be endogenous agonist ligands; opposed by sigma antagonistic activity fromprogesterone.[9] Another endogenous ligand,N,N-dimethyltryptamine, was also found to interact with σ1.[10][11]

Physiologic effects

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Physiologic effects when the σ-receptor is activated includehypertonia,tachycardia,tachypnea,antitussive effects, andmydriasis.[citation needed] Some σ-receptor agonists—such as cocaine, a weak σ-agonist—exert convulsant effects in animals.

In 2007, selective σ-receptor agonists were shown to produceantidepressant-like effects in mice.[12]

σ-receptors were also shown to have a role in the regulation of iron/heme homeostasis.[13]

Ligands

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Agonists

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Antagonists

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References

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  1. ^Yang S, Bhardwaj A, Cheng J, Alkayed NJ, Hurn PD, Kirsch JR (May 2007)."Sigma receptor agonists provide neuroprotection in vitro by preserving bcl-2".Anesthesia and Analgesia.104 (5):1179–84, tables of contents.doi:10.1213/01.ane.0000260267.71185.73.PMC 2596726.PMID 17456670.
  2. ^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):934–7.Bibcode:2009Sci...323..934F.doi:10.1126/science.1166127.PMC 2947205.PMID 19213917.
  3. ^Skuza G, Rogóz Z (June 2006). "The synergistic effect of selective sigma receptor agonists and uncompetitive NMDA receptor antagonists in the forced swim test in rats".Journal of Physiology and Pharmacology.57 (2):217–29.PMID 16845227.
  4. ^Sanchez-Pulido L, Ponting CP (2014)."TM6SF2 and MAC30, new enzyme homologs in sterol metabolism and common metabolic disease".Frontiers in Genetics.5: 439.doi:10.3389/fgene.2014.00439.PMC 4263179.PMID 25566323.
  5. ^Bartz F, Kern L, Erz D, Zhu M, Gilbert D, Meinhof T, Wirkner U, Erfle H, Muckenthaler M, Pepperkok R, Runz H (July 2009)."Identification of Cholesterol-Regulating Genes by Targeted RNAi Screening".Cell Metabolism.10 (1):63–75.doi:10.1016/j.cmet.2009.05.009.PMID 19583955.
  6. ^Kim FJ, Pasternak GW (2017). "Introduction to Sigma Proteins: Evolution of the Concept of Sigma Receptors".Sigma Proteins: Evolution of the Concept of Sigma Receptors. Handbook of Experimental Pharmacology. Vol. 244. Cham: Springer International Publishing. pp. 1–11.doi:10.1007/164_2017_41.ISBN 978-3-319-65853-7.PMID 28871306.
  7. ^Hanner M, Moebius FF, Flandorfer A, Knaus HG, Striessnig J, Kempner E, Glossmann H (July 1996)."Purification, molecular cloning, and expression of the mammalian sigma1-binding site".Proceedings of the National Academy of Sciences of the United States of America.93 (15):8072–7.Bibcode:1996PNAS...93.8072H.doi:10.1073/pnas.93.15.8072.PMC 38877.PMID 8755605.
  8. ^Leonard BE (November 2004). "Sigma receptors and sigma ligands: background to a pharmacological enigma".Pharmacopsychiatry.37 (Suppl 3): S166–70.doi:10.1055/s-2004-832674.PMID 15547782.S2CID 38914893.
  9. ^abMaurice T, Su TP (November 2009)."The pharmacology of sigma-1 receptors".Pharmacology & Therapeutics.124 (2):195–206.doi:10.1016/j.pharmthera.2009.07.001.PMC 2785038.PMID 19619582.
  10. ^Guitart X, Codony X, Monroy X (July 2004). "Sigma receptors: biology and therapeutic potential".Psychopharmacology.174 (3):301–19.doi:10.1007/s00213-004-1920-9.PMID 15197533.S2CID 23606712.
  11. ^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):934–7.Bibcode:2009Sci...323..934F.doi:10.1126/science.1166127.PMC 2947205.PMID 19213917.
  12. ^Wang J, Mack AL, Coop A, Matsumoto RR (November 2007)."Novel sigma (sigma) receptor agonists produce antidepressant-like effects in mice".European Neuropsychopharmacology.17 (11):708–16.doi:10.1016/j.euroneuro.2007.02.007.PMC 4041597.PMID 17376658.
  13. ^Nguyen NT, Jaramillo-Martinez V, Mathew M, Suresh VV, Sivaprakasam S, Bhutia YD, Ganapathy V (January 2023)."Sigma Receptors: Novel Regulators of Iron/Heme Homeostasis and Ferroptosis".International Journal of Molecular Sciences.24 (19): 14672.doi:10.3390/ijms241914672.ISSN 1422-0067.PMC 10572259.PMID 37834119.
  14. ^"Researchers identify long-sought activator of sigma receptors in human cells". 2019-01-14. Retrieved2022-03-14.
  15. ^"(ACMD) Methoxetamine Report (2012)"(PDF).UK Home Office. 2012-10-18. p. 14. Retrieved2012-10-22.
  16. ^Vollenweider FX, Leenders KL, Oye I, Hell D, Angst J (February 1997). "Differential psychopathology and patterns of cerebral glucose utilisation produced by (S)- and (R)-ketamine in healthy volunteers using positron emission tomography (PET)".European Neuropsychopharmacology.7 (1):25–38.doi:10.1016/S0924-977X(96)00042-9.PMID 9088882.S2CID 26861697.
  17. ^Klepstad P, Maurset A, Moberg ER, Oye I (October 1990). "Evidence of a role for NMDA receptors in pain perception".European Journal of Pharmacology.187 (3):513–8.doi:10.1016/0014-2999(90)90379-k.PMID 1963598.
  18. ^Calabrese JR,Suppes T, Bowden CL, Sachs GS, Swann AC, McElroy SL, Kusumakar V, Ascher JA, Earl NL, Greene PL, Monaghan ET (November 2000). "A double-blind, placebo-controlled, prophylaxis study of lamotrigine in rapid-cycling bipolar disorder. Lamictal 614 Study Group".The Journal of Clinical Psychiatry.61 (11):841–50.doi:10.4088/jcp.v61n1106.PMID 11105737.S2CID 71423264.
  19. ^Ng F, Hallam K, Lucas N, Berk M (August 2007)."The role of lamotrigine in the management of bipolar disorder".Neuropsychiatric Disease and Treatment.3 (4):463–74.PMC 2655087.PMID 19300575.
  20. ^Peeters M, Romieu P, Maurice T, Su TP, Maloteaux JM, Hermans E (April 2004). "Involvement of the sigma 1 receptor in the modulation of dopaminergic transmission by amantadine".The European Journal of Neuroscience.19 (8):2212–20.doi:10.1111/j.0953-816X.2004.03297.x.PMID 15090047.S2CID 19479968.
  21. ^Zhang CL, Feng ZJ, Liu Y, Ji XH, Peng JY, Zhang XH, Zhen XC, Li BM (2012)."Methylphenidate enhances NMDA-receptor response in medial prefrontal cortex via sigma-1 receptor: a novel mechanism for methylphenidate action".PLOS ONE.7 (12): e51910.Bibcode:2012PLoSO...751910Z.doi:10.1371/journal.pone.0051910.PMC 3527396.PMID 23284812.
  22. ^Kamei J (Oct–Dec 1996). "Role of opioidergic and serotonergic mechanisms in cough and antitussives".Pulmonary Pharmacology.9 (5–6):349–56.doi:10.1006/pulp.1996.0046.PMID 9232674.
  23. ^Xu YT, Kaushal N, Shaikh J, Wilson LL, Mésangeau C, McCurdy CR, Matsumoto RR (May 2010)."A novel substituted piperazine, CM156, attenuates the stimulant and toxic effects of cocaine in mice".The Journal of Pharmacology and Experimental Therapeutics.333 (2):491–500.doi:10.1124/jpet.109.161398.PMC 2872963.PMID 20100904.
  24. ^Krutetskaya ZI, Melnitskaya AV, Antonov VG, Nozdrachev AD (May 2019). "Sigma-1 Receptor Antagonists Haloperidol and Chlorpromazine Modulate the Effect of Glutoxim on Na+ Transport in Frog Skin".Doklady. Biochemistry and Biophysics.484 (1):63–65.doi:10.1134/S1607672919010186.PMID 31012016.S2CID 126409347.
  25. ^Matsumoto RR, Gilmore DL, Pouw B, Bowen WD, Williams W, Kausar A, Coop A (May 2004). "Novel analogs of the sigma receptor ligand BD1008 attenuate cocaine-induced toxicity in mice".Eur J Pharmacol.492 (1):21–6.doi:10.1016/j.ejphar.2004.03.037.PMID 15145701.
  26. ^Daniels A, Ayala E, Chen W, Coop A, Matsumoto RR (August 2006). "N-[2-(m-methoxyphenyl)ethyl]-N-ethyl-2-(1-pyrrolidinyl)ethylamine (UMB 116) is a novel antagonist for cocaine-induced effects".Eur J Pharmacol.542 (1–3):61–8.doi:10.1016/j.ejphar.2006.03.062.PMID 16797004.
  27. ^Tapia MA, Sage AS, Fullerton EI, Judd JM, Hildebrant PC, Will MJ, Lever SZ, Lever JR, Miller DK (March 2020). "The sigma receptor ligand N-phenylpropyl-N'-(4-methoxyphenethyl)3piperazine (YZ-067) enhances the cocaine conditioned-rewarding properties while inhibiting the development of sensitization of cocaine in mice".Psychopharmacology (Berl).237 (3):723–734.doi:10.1007/s00213-019-05411-z.PMID 31822924.
  28. ^Matsumoto RR, Potelleret FH, Mack A, Pouw B, Zhang Y, Bowen WD (April 2004). "Structure-activity comparison of YZ-069, a novel sigma ligand, and four analogs in receptor binding and behavioral studies".Pharmacol Biochem Behav.77 (4):775–81.doi:10.1016/j.pbb.2004.01.014.PMID 15099923.
  29. ^Sage AS, Vannest SC, Fan KH, Will MJ, Lever SZ, Lever JR, Miller DK (2013)."N-Phenylpropyl-N'-(3-methoxyphenethyl)piperazine (YZ-185) Attenuates the Conditioned-Rewarding Properties of Cocaine in Mice".ISRN Pharmacol.2013: 546314.doi:10.1155/2013/546314.PMC 3780704.PMID 24089641.

External links

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G protein-coupled receptor
Hormone receptors
Hypothalamic
Pituitary
Other
Opioid receptors
Other neuropeptide receptors
Type I cytokine receptor
Enzyme-linked receptor
Other
σ1
σ2
Unsorted
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