Antinociception depends on the presence of G protein γ2- subunits in brain

Eva V. Varga, Keiko Hosohata, Dariusz Borys, Edita Navratilova, Anders Nylen, Todd W. Vanderah, Frank Porreca, William R. Roeske, Henry I. Yamamura

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

We have shown previously [Hosohata, K., Logan, J.K., Varga, E., Burkey, T.H., Vanderah, T.W., Porreca, F., Hruby, V.J., Roeske, W.R., Yamamura, H.I., 2000. The role of the G protein γ2 subunit in opioid antinociception in mice. Eur. J. Pharmacol. 392, R9-R11] that intracerebroventricular (i.c.v.) treatment of mice with a phosphorothioate oligodeoxynucleotide antisense to the γ2 subunit (Gγ2) of the heterotrimeric G proteins (antisense ODN) significantly attenuates antinociception by a δ-opioid receptor agonist. In the present study, we examined the involvement of Gγ2 in antinociception mediated by other (μ- or κ-opioid, cannabinoid, α2-adrenoreceptor) analgesic agents in a warm (55°C) water tail-flick test in mice. Interestingly, i.c.v. treatment with the antisense ODN attenuated antinociception by each analgesic agent. Missense phosphorothioate oligodeoxynucleotide treatment, on the other hand, had no effect on antinociception mediated by these agonists. The antinociceptive response recovered in 6 days after the last antisense ODN injection, indicating a lack of nonspecific tissue damage in the animals. These results suggest a pervasive role for the G protein γ2 subunits in supraspinal antinociception.

Original languageEnglish (US)
Pages (from-to)93-98
Number of pages6
JournalEuropean Journal of Pharmacology
Volume508
Issue number1-3
DOIs
StatePublished - Jan 31 2005

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Keywords

  • Antinociception
  • Cannabinoid receptor agonist
  • Clonidine
  • G protein γ subunit
  • Guanine nucleotide binding protein
  • Opioid receptor agonist

ASJC Scopus subject areas

  • Pharmacology

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