Alpha-subunit G-protein antisense oligodeoxynucleotide effects on supraspinal (i.c.v.) alpha2-adrenoceptor...

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.