MASTOPARAN REDUCES THE SUPRASPINAL ANALGESIA MEDIATED BY MU/DELTA-OPIOID RECEPTORS IN MICE

Intracerebroventricular (i.c.v.) administration of the venom peptide, mastoparan, to mice decreased to a limited extent opioid-induced supraspinal analgesia in a non-competitive fashion. The mu-opioid receptor agonists, [D-Ala(2),N-MePhe(4),Gly-ol(5)]enkephalin (DAMGO) and morphine, the mu/delta-opioid receptor ligands, human beta-endorphin-(1-31) and [D-Ala(2),D-Leu(5)]enkephalin (DADLE), and the selective ligands of delta-opioid receptors, [D-Pen(2,5)]enkephalin (DPDPE) and [D-Ala(2)]deltorphin II, showed an impaired analgesic effect in mice given mastoparan. Mastoparan diminished the analgesic activity of DPDPE and [D-Ala(2)]deltorphin II to the same extent as observed after giving the delta-opioid receptor-selective antagonist, ICI 174864. The mu-opioid receptor-mediated analgesia that remained after mastoparan was abolished in the presence of the opioid antagonist, naloxone. Mastoparan after binding to G(i) alpha/G(0) alpha subunits could block opioid antinociception. The existence of a class of G protein functionally coupled to mu-opioid receptors, but resistant to the effect of mastoparan is suggested.