The role of the G protein γ2 subunit in opioid antinociception in mice

We examined the role of the gamma(2) subunit of G proteins (G gamma(2)) in the antinociception produced by c[D-Pen(2),D- Pen(5)]enkephalin (DPDPE) in mice. DPDPE produced 84.0 +/- 9.0% antinociception in vehicle-treated mice. After intracerebroventricular (i.c.v.) treatment with an antisense phosphorothioate oligodeoxynucleotide to the G gamma(2) subunit, DPDPE-mediated antinociception decreased to 24.4 +/- 7.4%. The mismatch phosphorothioate oligodeoxynucleotide-treated mice showed 65.1 +/- 10.3% antinociception, while the missense phosphorothioate oligodeoxynucleotide-treated mice showed 76.4 +/- 23.6% antinociception by DPDPE. The reduction of analgesia in antisense phosphorothioate oligodeoxynucleotide-treated mice was significant in comparison with vehicle-treated (P < 0.001), mismatch phosphorothioate oligodeoxynucleotide-treated (P < 0.01) and missense phosphorothioate oligodeoxynucleotide-treated (P < 0.05) mice. These results suggest that the G protein gamma(2) subunit is involved in the transduction pathway leading to antinociception by DPDPE. (C) 2000 Published by Elsevier Science B.V. All rights reserved.