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(i2)α 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(i1)α subunits did not modify this opioid activity. In mice injected with sera anti-G(X/Z)α, 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-Ala2] 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(i2)α and anti-G(X/Z)α, but not anti-G(i1)α, reduced the 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.