title: 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.forename: Michael J
authors.initials: MJ
authors.lastname: Iadarola
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Sapio
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Mannes
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D017450:Receptors, Opioid, mu / Q000235:genetics* / Q000502:physiology*
chemical_list: D000701:Analgesics, Opioid; D017450:Receptors, Opioid, mu