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A new splice of life for the μ-opioid receptor
Michael J. Iadarola, … , Matthew R. Sapio, Andrew J. Mannes
Michael J. Iadarola, … , Matthew R. Sapio, Andrew J. Mannes
Published May 26, 2015
Citation Information: J Clin Invest. 2015;125(7):2558-2561. https://doi.org/10.1172/JCI82060.
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Commentary

A new splice of life for the μ-opioid receptor

Abstract

μ-Opioid agonists mediate their analgesic effect through GPCRs that are generated via alternate splicing of the Oprm1 transcript. While the majority of μ-opioids interact with receptors comprising the canonical 7 transmembrane (7TM) domain, a recently identified class of μ-opioids appears to require a 6TM domain variant. In this issue of the JCI, Lu and colleagues provide an in vivo proof-of-concept demonstration that a 6TM isoform of the μ-opioid receptor can support functional analgesia in Oprm1-deficent animals. The 6TM isoform was pharmacologically distinct from the canonical 7TM μ-opioid receptor, and 6TM agonists had a reduced side effect profile, which confers a strong therapeutic advantage over standard opioid analgesics. The observations of Lu et al. extend the reach of opioid-receptor neurobiology and pharmacology into a new era of analgesic discovery. This advance emerges from a series of fundamental research analyses in which elements of the endogenous opioid system were frequently in the vanguard.

Authors

Michael J. Iadarola, Matthew R. Sapio, Andrew J. Mannes

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