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

J. Lai, E. J. Bilsky, R. B. Rothman, Frank Porreca

Research output: Contribution to journalArticle

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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 δ 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,Glu4]deltorphin (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 antisense 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]deltorphin.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
StatePublished - 1994

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D-Penicillamine (2,5)-Enkephalin
Oligodeoxyribonucleotides
Opioid Receptors
Pharmacology
deltorphin

Keywords

  • [D-Ala,Glu]deltorphin
  • antinociception
  • antisense oligodeoxynucleotides
  • DPDPE
  • mouse
  • opioid δ receptor subtypes

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Treatment with antisense oligodeoxynucleotide to the opioid δ receptor selectively inhibits δ2-agonist antinociception. / Lai, J.; Bilsky, E. J.; Rothman, R. B.; Porreca, Frank.

In: NeuroReport, Vol. 5, No. 9, 1994, p. 1049-1052.

Research output: Contribution to journalArticle

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