G(X Z) AND G(I2) TRANSDUCER PROTEINS ON MU/DELTA OPIOID-MEDIATED SUPRASPINAL ANTINOCICEPTION/

Intracerebroventricular (i.c.v.) administration of immune sera raised against G(i2)alpha subunits to mice, significantly reduced the suprasp inal antinociceptive effect of opioids when evaluated 24 h later in th e tail-flick test. Antisera directed against G(i1)alpha subunits did n ot modify this opioid activity. In mice injected with sera anti-G(x/z) alpha, the p-preferential agonists, DAMGO and morphine, and the endoge nous mu/delta opioid peptide beta-endorphin-(1-31) displayed a reduced antinociceptive activity, whereas, the potency of the delta-selective agonists DPDPE and [D-Ala2] Deltorphin II, was not altered. This redu ction was present for 3 to 7 days and returned to the control values a fter 10 days. Anti-G(i2)alpha and anti-G(x/z)alpha, but not anti-G(i1) alpha, reduced the specific binding of [H-3]DAMGO to the opioid recept or in PAG. These results suggest the ability of the mu receptor to int eract in vivo with different classes of G transducer proteins (G(x/z)/ G(i2)) to produce an effect. This work also indicates a functional rol e of the pertussis toxin insensitive G(x/z) protein, on the mu-mediate d (but not delta-mediated) supraspinal antinociception in mice.