Alpha-subunit G-protein antisense oligodeoxynucleotide effects on supraspinal (i.c.v.) alpha2-adrenoceptor antinociception in mice.
An in vivo antisense strategy was used to examine the involvement of G-protein subunits in supraspinal (intracerebroventricular; i.c.v.) alpha2-adrenoceptor-mediated antinociception. Mice that were injected with 33-mer antisense oligodeoxyribonucleotides (6 nmol) or vehicle were tested (tail-flick) with an agonist (clonidine, guanfacine or BH-T 920) administered i.c.v. 18 - 24 h later. Gi3alpha antisense treatment attenuated BH-T 920 and clonidine-induced antinociception. Gi2alpha antisense produced differential effects on the three agonists. Gi1alpha and G(s)alpha antisense treatment had no significant effect. Together with the previous demonstration that i.c.v. mu-opioid antinociception is mediated via Gi2alpha, the present results suggest that different receptors may mediate antinociception via different G-protein subunits and, hence, that specific subunits might offer novel targets for drug discovery.
Raffa
R B
RB
Drug Discovery Research, The R.W. Johnson Pharmaceutical Research Institute, Spring House, PA, USA.
Connelly
C D
CD
Chambers
J R
JR
Stone
D J
DJ
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D001483:Base Sequence; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D003000:Clonidine / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000235:genetics*; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000494:pharmacology*; D010146:Pain; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D001381:Azepines; D015345:Oligonucleotide Probes; D016376:Oligonucleotides, Antisense; D018341:Receptors, Adrenergic, alpha-2; C024763:talipexole; D019204:GTP-Binding Proteins; D003000:Clonidine