Sigma receptor

Source: Wikipedia, the free encyclopedia.
ERG2/Sigma-1 receptor
Identifiers
SymbolERG2_Sigma1R
TCDB
8.A.63
OPM superfamily446
OPM protein5hk1
Membranome1025
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
Sigma intracellular receptor 2
Identifiers
SymbolSigma2
InterProIPR016964

Sigma receptors (σ-receptors) are

dimethyltryptamine,[2] and siramesine.[3] There are two subtypes, sigma-1 receptors (σ1) and sigma-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 same

ER membrane, although sigma-1 is also reported to be a cell surface receptor. Sigma-2 is an EXPREA domain protein[4] with a mostly intracellular (ER membrane) localization.[5]

Classification

Because the σ-receptor was originally discovered to be agonized by benzomorphan opioids and antagonized by naltrexone, 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

The function of these receptors is poorly understood.

diacetylmorphine, opipramol, PCP, fluvoxamine, methamphetamine, dextromethorphan, and berberine.[citation needed] However, the exact role of σ-receptors is difficult to establish as many σ-agonists also bind to other targets such as the κ-opioid receptor and the NMDA glutamate receptor. In animal experiments, σ-antagonists such as rimcazole were able to block convulsions from cocaine overdose. σ-antagonists are also under investigation for use as antipsychotic
medications.

The abundant neurosteroid steroid hormone

DHEA is an agonist at sigma receptors and along with pregnenolone could be endogenous agonist ligands; opposed by sigma antagonistic activity from progesterone.[9] Another endogenous ligand, N,N-dimethyltryptamine, was also found to interact with σ1.[10][11]

Physiologic effects

Physiologic effects when the σ-receptor is activated include

antitussive effects, and mydriasis.[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 produce antidepressant-like effects in mice.[12]

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

Ligands

Agonists

Antagonists

References

  1. PMID 17456670
    .
  2. PMID 19213917
    .
  3. PMID 16845227
    .
  4. PMID 25566323
    .
  5. PMID 19583955
    .
  6. PMID 28871306
    .
  7. PMID 8755605
    .
  8. S2CID 38914893
    .
  9. ^
    PMID 19619582
    .
  10. S2CID 23606712
    .
  11. PMID 19213917
    .
  12. PMID 17376658
    .
  13. PMID 37834119
    .
  14. ^ "Researchers identify long-sought activator of sigma receptors in human cells". 2019-01-14. Retrieved 2022-03-14.
  15. ^ "(ACMD) Methoxetamine Report (2012)" (PDF). UK Home Office. 2012-10-18. p. 14. Retrieved 2012-10-22.
  16. S2CID 26861697
    .
  17. PMID 1963598
    .
  18. S2CID 71423264
    .
  19. PMID 19300575
    .
  20. S2CID 19479968
    .
  21. PMID 23284812
    .
  22. PMID 9232674
    .
  23. PMID 20100904
    .
  24. S2CID 126409347
    .

External links
Retrieved from "https://en.wikipedia.org/w/index.php?title=Sigma_receptor&oldid=1214118245"