The role of the G protein gamma(2) subunit in opioid antinociception in mice.
We examined the role of the gamma(2) subunit of G proteins (Ggamma(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 Ggamma(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.
Hosohata
K
K
Departments of Pharmacology, Chemistry, Biochemistry, Psychiatry, Medicine and the Program in Neuroscience, University of Arizona, Tucson, AZ 85724, USA.
Logan
J K
JK
Varga
E
E
Burkey
T H
TH
Vanderah
T W
TW
Porreca
F
F
Hruby
V J
VJ
Roeske
W R
WR
Yamamura
H I
HI
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000494:pharmacology*; D020962:Heterotrimeric GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009154:Mutation; D009619:Nociceptors / Q000187:drug effects*; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology / Q000517:prevention & control*; D010147:Pain Measurement; D013873:Thionucleotides / Q000235:genetics / Q000494:pharmacology
D000701:Analgesics, Opioid; D016376:Oligonucleotides, Antisense; D013873:Thionucleotides; D020881:Enkephalin, D-Penicillamine (2,5)-; D020962:Heterotrimeric GTP-Binding Proteins