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Allosteric Modulation of Opioid G-Protein Coupled Receptors by Sigma1 Receptors

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Book cover Sigma Proteins: Evolution of the Concept of Sigma Receptors

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 244))

Abstract

Since their proposal in 1976, the concept of sigma1 receptors has been continually evolving. Initially thought to be a member of the opioid receptor family, molecular studies have now identified its genes and established its structure crystallographically. Much effort has now revealed its importance as a chaperone in the endoplasmic reticulum, but its functions extend beyond this. Sigma1 receptors have been associated with a host of signaling systems. Evidence over the past 20 years has established the modulatory effects of sigma1 ligands on opioid systems. Despite their inability to bind directly to opioid receptors, sigma1 ligands can modulate opioid analgesia in vivo and signal transduction mechanisms in vitro. Furthermore, sigma1 receptors can physically associate with GPCRs. Together, these findings show that sigma1 ligands can function as allosteric modulators of GPCR function through their association with the sigma1 receptors, which are in direct physical association with opioid receptors, members of the G-protein coupled family of receptors.

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Acknowledgements

The work described was supported, in part, by research grants (DA7242 and DA6241) from the National Institute on Drug Abuse and a Core Grant (CA08748) from the National Cancer Institute to MSKCC.

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Authors and Affiliations

  1. Department of Neurology and Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10021, USA

    Gavril W. Pasternak

  2. Department of Neurology, Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065, USA

    Gavril W. Pasternak

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  1. Gavril W. Pasternak
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Correspondence to Gavril W. Pasternak .

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Editors and Affiliations

  1. Pharmacology & Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA

    Felix J. Kim

  2. Molecular Pharmacology and Chemistry, Memorial Sloan-Kettering Cancer Center, New York, New York, USA

    Gavril W. Pasternak

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Pasternak, G.W. (2017). Allosteric Modulation of Opioid G-Protein Coupled Receptors by Sigma1 Receptors. In: Kim, F., Pasternak, G. (eds) Sigma Proteins: Evolution of the Concept of Sigma Receptors. Handbook of Experimental Pharmacology, vol 244. Springer, Cham. https://doi.org/10.1007/164_2017_34

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