Treatment with antisense oligodeoxynucleotide to the opioid δ receptor selectively inhibits δ2-agonist antinociception

Josephine Lai, Edward J. Bilsky, Richard B. Rothman, Frank Porreca

Research output: Contribution to journalArticle

75 Scopus citations

Abstract

Using approaches emphasizing differential antagonism of receptor selective agonists and cross-tolerance paradigms, evidence in vivo has suggested the existence of subtypes of opioid δ receptors, which have been termed δ1 and δ2. Recent work has elucidated the structure of an opioid δ receptor. The present investigation attempted to continue to test the hypothesis of subtypes of 5 receptors and to correlate the cloned δ receptor with the existing pharmacological classification. Synthetic oligodeoxynucleotides (oligos) complementary to the 5' end of the cloned δ receptor coding region (antisense) or its corresponding sequence (sense) were given by intracerebroventricular (i.c.v.) administration to mice, twice-daily for 3 days and antinociceptive responses to selective agonists at putative δ1 and δ2 receptors were subsequently determined. Treatment with antisense, but not sense, oligo significantly inhibited the response to [D-Ala2, GIu4]deItorphin (δ2 agonist), but not to [D-Pen2, D-Pen5]enkephalin (DPDPE, δ1 agonist). Further, subsequent administration of DPDPE elicited a full antinociceptive response in the same anti-sense oligo treated mice which did not show a significant response to [D-Ala2, Glu4]deltorphin while antisense oligo treated mice which responded to DPDPE did not show antinociception when tested subsequently with [D-Ala2, Glu4]deItorphin. The data suggest that the cloned δ receptor corresponds to that pharmacologically classified as δ2 and continue to support the concept of subtypes of opioid δ receptors.

Original languageEnglish (US)
Pages (from-to)1049-1052
Number of pages4
JournalNeuroReport
Volume5
Issue number9
DOIs
StatePublished - May 1994

    Fingerprint

Keywords

  • Antinociception
  • Antisense oligodeoxynucleotides
  • DPDPE, [D-Ala, Glu]deltorphin
  • Mouse
  • Opioid δ receptor subtypes

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this