Pertussis toxin abolishes the antinociception mediated by opioid receptors in rat spinal cord.

Intrathecal injection of pertussis toxin (1 microgram) in rats produced a marked decrease in the antinociceptive effect of the intrathecally administered opioid agonists [D-Ala2,D-Leu5]enkephalin, [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin and bremazocine. The effect of the toxin was time-dependent, since it was more pronounced at 6 than at 2 days after its injection. The pertussis toxin-catalyzed ADP ribosylation of a 40 KDa substrate in membranes prepared from the spinal cord of toxin-injected rats was strongly reduced as compared to controls. The data indicate that the antinociceptive effect produced by opioid agonists with different receptor preference is initiated at receptor sites which interact with G-protein substrates of pertussis toxin.