The fungal protein ERG2, a C-8 sterol isomerase, falls into the same
protein family as sigma-1. Both localize to the
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
benzomorphanopioids 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.
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]
^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.
PMID16845227.
^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.
ISBN978-3-319-65853-7.
PMID28871306.
^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.
PMID9088882.
S2CID26861697.
^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.
PMID1963598.
^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.
PMID11105737.
S2CID71423264.
^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.
PMID15090047.
S2CID19479968.
^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.
PMID31012016.
S2CID126409347.