G X/Z and G i2 transducer proteins on μ/δ opioid-mediated supraspinal antinociception

Abstract

Intracerebroventricular (i.c.v.) administration of immune sera raised against G i2α subunits to mice, significantly reduced the supraspinal antinociceptive effect of opioids when evaluated 24 h later in the tail-flick test. Antisera directed against G i1α subunits did not modify this opioid activity. In mice injected with sera anti-G X/Zα, the μ-preferential agonists, DAMGO and morphine, and the endogenous μ/δ opioid peptide β-endorphin-(1–31) displayed a reduced antinociceptive activity, whereas, the potency of the δ-selective agonists DPDPE and [D-Ala 2] Deltorphin II, was not altered. This reduction was present for 3 to 7 days and returned to the control values after 10 days. Anti-G i2α and anti-G X/Zα, but not anti-G i1α, reduced the e specific binding of [ 3H]DAMGO to the opioid receptor in PAG. These results suggest the ability of the μ receptor to interact in vivo with different classes of G transducer proteins (G X/Z/G i2) to produce an effect. This work also indicates a functional role of the pertussis toxin insensitive G X/Z protein, on the μ-mediated (but not δ-mediated) supraspinal antinociception in mice.