Antisense oligodeoxynucleotide to a delta-opioid receptor selectively blocks the spinal antinociception induced by delta-, but not mu- or kappa-opioid receptor agonists in the mouse

Eur J Pharmacol. 1994 Jun 2;258(1-2):R1-3. doi: 10.1016/0014-2999(94)90072-8.

Abstract

An antisense oligodeoxynucleotide (A-oligo) to delta-opioid receptor mRNA was utilized to block the expression of mouse delta-opioid receptor in the spinal cord of male ICR mice. Intrathecal treatment with A-oligo (1.6-163 pmol) dose-dependently attenuated the antinociception induced by i.t. administered DPDPE ([D-Pen2,5]enkephalin) or [D-Ala2]deltorphin II, delta-opioid receptor agonist, without affecting the antinociception induced by DAMGO ([D-Ala2-MePhe4,Gly(ol)5]enkephalin) or U50,488H, respective mu- or kappa-opioid receptor agonists. Scrambled sense oligodeoxynucleotide (163 pmol) was ineffective against the tail-flick inhibition induced by DPDPE,[D-Ala2]deltorphin, DAMGO or U50,488H. The studies confirm previous pharmacological studies at the molecular level indicating a distinct delta-opioid receptor for antinociception in the spinal cord.

Publication types

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

MeSH terms

  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • Analgesics / antagonists & inhibitors*
  • Analgesics / pharmacology
  • Animals
  • Base Sequence
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Enkephalin, D-Penicillamine (2,5)-
  • Enkephalins / antagonists & inhibitors
  • Enkephalins / pharmacology
  • Male
  • Mice
  • Molecular Sequence Data
  • Oligonucleotides, Antisense / genetics
  • Oligonucleotides, Antisense / pharmacology*
  • Pyrrolidines / antagonists & inhibitors
  • Pyrrolidines / pharmacology
  • RNA, Messenger / metabolism
  • Receptors, Opioid, delta / antagonists & inhibitors*
  • Receptors, Opioid, delta / genetics
  • Receptors, Opioid, delta / metabolism
  • Receptors, Opioid, kappa / antagonists & inhibitors
  • Receptors, Opioid, kappa / metabolism
  • Receptors, Opioid, mu / antagonists & inhibitors
  • Receptors, Opioid, mu / metabolism

Substances

  • Analgesics
  • Enkephalins
  • Oligonucleotides, Antisense
  • Pyrrolidines
  • RNA, Messenger
  • Receptors, Opioid, delta
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • Enkephalin, D-Penicillamine (2,5)-