Mastoparan reduces the supraspinal analgesia mediated by μ/δ-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 μ-opioid receptor agonists, [D-Ala2,N-MePhe4,Gly-ol5]-enkephalin (DAMGO) and morphine, the μ/δ-opioid receptor ligands, human β-endorphin-(1-31) and [D-Ala2,D-Leu5]-enkephalin (DADLE), and the selective ligands of δ-opioid receptors, [D-Pen2,5]enkephalin (DPDPE) and [D-Ala2]deltorphin II, showed an impaired analgesic effect in mice given mastoparan. Mastoparan diminished the analgesic activity of DPDPE and [D-Ala2]deltorphin II to the same extent as observed after giving the δ-opioid receptor-selective antagonist, ICI 174864. The μ-opioid receptor-mediated analgesia that remained after mastoparan was abolished in the presence of the opioid antagonist, naloxone. Mastoparan after binding to G(i)α/G(o)α subunits could block opioid antinociception. The existence of a class of G protein functionally coupled to μ-opioid receptors, but resistant to the effect of mastoparan is suggested.Peer Reviewe