G-protein antisense oligodeoxyribonucleotides and mu-opioid supraspinal antinociception

Eur J Pharmacol. 1994 Jun 2;258(1-2):R5-7. doi: 10.1016/0014-2999(94)90073-6.


The present study utilized an in vivo antisense strategy to examine the functional interaction of supraspinal mu-opioid receptors with the G protein subunits Gi1 alpha, Gi2 alpha, Gi3 alpha and Gs alpha. Mice were injected intracerebroventricularly (i.c.v.) with 33-base phosphorothioate oligodeoxyribonucleotides (12.5 micrograms) or with vehicle in equal volume (sterile water, 5 microliters) and the antinociceptive responses to i.c.v. morphine [D-Ala2,NMePhe4,Gly5-ol]enkephalin (DAMGO) or sufentanil were determined 18-24 h later using the tail-flick test. Treatment with antisense to Gi2 alpha, but not the other subunits, significantly attenuated morphine-induced antinociception. The degree of attenuation for the three mu-opioid agonists was in the order morphine > DAMGO > sufentanil, the inverse of their intrinsic efficacy.

MeSH terms

  • Analgesics / pharmacology*
  • Animals
  • Base Sequence
  • Drug Interactions
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Enkephalins / pharmacology
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism*
  • Injections, Intraventricular
  • Male
  • Mice
  • Molecular Sequence Data
  • Morphine / pharmacology
  • Oligonucleotides, Antisense / administration & dosage
  • Oligonucleotides, Antisense / pharmacology*
  • Receptors, Opioid, mu / drug effects
  • Receptors, Opioid, mu / metabolism*
  • Sufentanil / pharmacology


  • Analgesics
  • Enkephalins
  • Oligonucleotides, Antisense
  • Receptors, Opioid, mu
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Morphine
  • Sufentanil
  • GTP-Binding Proteins