Antinociception depends on the presence of G protein gamma2-subunits in brain.
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 gamma2 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 gamma2 subunit (Ggamma2) of the heterotrimeric G proteins (antisense ODN) significantly attenuates antinociception by a delta-opioid receptor agonist. In the present study, we examined the involvement of Ggamma2 in antinociception mediated by other (mu- or kappa-opioid, cannabinoid, alpha2-adrenoreceptor) analgesic agents in a warm (55 degrees 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 gamma2 subunits in supraspinal antinociception.
Varga
Eva V
EV
Department of Pharmacology, and the Sarver Heart Center, University of Arizona, Tucson, Arizona 85724, USA.
Hosohata
Keiko
K
Borys
Dariusz
D
Navratilova
Edita
E
Nylen
Anders
A
Vanderah
Todd W
TW
Porreca
Frank
F
Roeske
William R
WR
Yamamura
Henry I
HI
D000700:Analgesics / Q000008:administration & dosage* / Q000627:therapeutic use; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D048588:Benzoxazines; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003000:Clonidine / Q000008:administration & dosage / Q000627:therapeutic use; D019204:GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000008:administration & dosage / Q000627:therapeutic use; D009025:Morpholines / Q000008:administration & dosage / Q000627:therapeutic use; D009281:Naphthalenes / Q000008:administration & dosage / Q000627:therapeutic use; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use; D009842:Oligopeptides / Q000008:administration & dosage / Q000627:therapeutic use; D010146:Pain / Q000517:prevention & control; D010147:Pain Measurement; D013997:Time Factors
D000700:Analgesics; D000701:Analgesics, Opioid; D048588:Benzoxazines; C410342:GNG2 protein, human; D009025:Morpholines; D009281:Naphthalenes; D016376:Oligonucleotides, Antisense; D009842:Oligopeptides; C060209:deltorphin II, Ala(2)-; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D009020:Morphine; D019204:GTP-Binding Proteins; D003000:Clonidine