Treatment with antisense oligodeoxynucleotide to a conserved sequence of opioid receptors inhibits antinociceptive effects of delta subtype selective ligands

J. Lai, E. J. Bilsky, F. Porreca

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Previous work has suggested the existence of subtypes of the delta opioid receptor (DOR) which have been termed δ1 and δ2. [D-Ala2, Glu4]deltorphin has been suggested to selectively elicit antinociception via the δ2 receptor while [D-Pen2, D-Pen5]enkephalin (DPDPE) is thought to act via the δ1 receptor. Treatment with an antisense oligodeoxynucleotide (oligo) directed towards the N-terminal portion of the cloned DOR has been demonstrated to selectively inhibit the antinociceptive actions of [D-Ala2, Glu4]deltorphin, but not of DPDPE, suggesting that the cloned DOR corresponds to that pharmacologically defined as δ2. Here, an antisense oligo (or a mismatch sequence) was designed to target a conserved region of the cloned μ δ and opioid receptor. These oligos were employed in order to determine whether the antinociceptive effects of [DAla2, Glu4]deltorphin, as well as DPDPE, could be inhibited. The data indicate that the antinociceptive actions of both ligands were inhibited by treatment with this antisense, but not with the mismatch oligo. Taken together, the results of the treatments with oligos directed towards the N-terminal portion of the cloned DOR and with that directed to the conserved region of the opioid receptors suggest that (a) DPDPE effects are mediated by a subtype of the DOR which shares a domain common to the cloned opioid receptors, and (b) the N-terminal region differs between these putative DOR subtypes.

Original languageEnglish (US)
Pages (from-to)643-650
Number of pages8
JournalJournal of Receptors and Signal Transduction
Volume15
Issue number1-4
DOIs
StatePublished - Jan 1 1995

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this