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Molecular Assays for Characterization of Alternatively Spliced Isoforms of the Mu Opioid Receptor (MOR)

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Analgesia

Part of the book series: Methods in Molecular Biology ((MIMB,volume 617))

Abstract

Mu-opioid receptor (MOR) belongs to a family of heptahelical G-protein-coupled receptors (GPCRs). Studies in humans and rodents demonstrated that the OPRM1 gene coding for MOR undergoes extensive alternative splicing afforded by the genetic complexity of OPRM1. Evidence from rodent studies also demonstrates an important role of these alternatively spliced forms in mediating opiate analgesia via their differential signaling properties. MOR signaling is predominantly Gia coupled. Release of the α subunit from G-protein complex results in the inhibition of adenylyl cyclase/cAMP pathway, whereas release of the βγ subunits activates G-protein-activated inwardly rectifying potassium channels and inhibits voltage-dependent calcium channels. These molecular events result in the suppression of cellular activities that diminish pain sensations. Recently, a new isoform of OPRM1, MOR3, has been identified that shows an increase in the production of nitric oxide (NO) upon stimulation with morphine. Hence, there is a need to describe molecular techniques that enable the functional characterization of MOR isoforms. In this review, we describe the methodologies used to assay key mediators of MOR activation including cellular assays for cAMP, free Ca2+, and NO, all of which have been implicated in the pharmacological effects of MOR agonists.

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Author information

Authors and Affiliations

  1. Center for Neurosensory Disorders, University of North Carolina, Chapel Hill, NC, USA

    Pavel Gris, Philip Cheng & John Pierson

  2. Center for Neurosensory Disorders, Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    William Maixner & Luda Diatchenko

Authors
  1. Pavel Gris
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  2. Philip Cheng
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  3. John Pierson
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  4. William Maixner
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  5. Luda Diatchenko
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Corresponding author

Correspondence to Luda Diatchenko .

Editor information

Editors and Affiliations

  1. Dept. Pathology, Monmouth Medical Center, Second Ave. 300, Long Branch, 07750, USA

    Arpad Szallasi

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Gris, P., Cheng, P., Pierson, J., Maixner, W., Diatchenko, L. (2010). Molecular Assays for Characterization of Alternatively Spliced Isoforms of the Mu Opioid Receptor (MOR). In: Szallasi, A. (eds) Analgesia. Methods in Molecular Biology, vol 617. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-323-7_30

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  • DOI: https://doi.org/10.1007/978-1-60327-323-7_30

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60327-322-0

  • Online ISBN: 978-1-60327-323-7

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