Blockade of morphine analgesia by an antisense oligodeoxynucleotide against the mu receptor

Grace Rossi, Ying Xian Pan, Jie Cheng, Gavril W. Pasternak

Research output: Contribution to journalArticlepeer-review

100 Scopus citations

Abstract

The recent cloning of mu, delta and kappa1, opioid receptors has provided opportunities in the study of their pharmacology. Using an antisense strategy developed against delta and kappa1 opioid receptors, we designed an antisense oligodeoxynucleotide directed against the 5′-untranslated region of MOR-1 clone, 51-70 bp upstream from the initiating ATG. Microinjection of this antisense oligodeoxynucleotide directly into the periaqueductal gray on Days 1, 3 and 5 completely blocked the analgesic actions of morphine administered into the periaqueductal gray on Day 6 (p < 0.001), 24 hr after the last antisense treatment. Rats treated with vehicle or with a mismatch oligodeoxynucleotide in which two pairs of bases from the antisense sequence had been switched were not significantly affected. These findings confirm the pharmacological relevance of the MOR-1 clone and its involvement in morphine's actions.

Original languageEnglish (US)
Pages (from-to)PL375-PL379
JournalLife Sciences
Volume54
Issue number21
DOIs
StatePublished - 1994
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Keywords

  • MOR-1 clone
  • antisense treatment
  • morphine
  • mu opioid receptor

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