Antisense mapping the MOR-1 opioid receptor: evidence for alternative splicing and a novel morphine-6 beta-glucuronide receptor

FEBS Lett. 1995 Aug 7;369(2-3):192-6. doi: 10.1016/0014-5793(95)00757-z.


Although MOR-1 encodes a mu opioid receptor, its relationship to the pharmacologically defined mu receptor subtypes has been unclear. Antisense mapping now suggests that these subtypes result from alternative splicing of MOR-1. Three oligodeoxynucleotide probes targeting exon 1 and another oligodeoxynucleotide directed against the coding region of exon 4 block supraspinal morphine analgesia, a mu1 action, while five of six oligodeoxynucleotides directed against exons 2 and 3 are inactive. Inhibition of gastrointestinal transit and spinal morphine analgesia, two mu2 actions, are blocked only by the probe against exon 4 and not by those directed against exon 1. In contrast, the analgesic actions of the extraordinarily potent mu drug morphine-6 beta-glucuronide are blocked by six different antisense oligodeoxynucleotides targeting exons 2 and 3, but not by those acting on exons 1 or 4. These results suggest that the mu1 and mu2 receptor subtypes originally defined in binding and pharmacological studies result from alternative splicing of MOR-1 while morphine-6 beta-glucuronide acts through a novel, previously unidentified receptor which is yet another MOR-1 splice variant.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alternative Splicing*
  • Analgesia
  • Animals
  • Base Sequence
  • Cloning, Molecular
  • DNA Probes
  • DNA, Antisense / genetics
  • DNA, Antisense / pharmacology*
  • Exons
  • Gastrointestinal Transit / drug effects
  • Male
  • Mice
  • Molecular Sequence Data
  • Morphine / pharmacology
  • Morphine Derivatives* / pharmacology
  • Nucleic Acid Heteroduplexes / genetics
  • Receptors, Opioid, mu / drug effects
  • Receptors, Opioid, mu / genetics*


  • DNA Probes
  • DNA, Antisense
  • Morphine Derivatives
  • Nucleic Acid Heteroduplexes
  • Receptors, Opioid, mu
  • morphine-6-glucuronide
  • Morphine

Associated data

  • GENBANK/U26915