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-Ala2,N-MePhe4,Gly-ol5]-enkephalin (DAMGO) and morphine, the mu/delta-opioid receptor ligands, human beta-endorphin-(1-31) and [D-Ala2,D-Leu5]-enkephalin (DADLE), and the selective ligands of delta-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 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 Gi alpha/Go 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.
Sánchez-Blázquez
P
P
Instituto Cajal, CSIC, Madrid, Spain.
Garzón
J
J
D000595:Amino Acid Sequence; D000700:Analgesics / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D016308:Enkephalin, Leucine-2-Alanine / Q000494:pharmacology; D004745:Enkephalins / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D007276:Injections, Intraventricular; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides; D011957:Receptors, Opioid / Q000187:drug effects* / Q000378:metabolism; D014862:Wasp Venoms / Q000008:administration & dosage / Q000494:pharmacology*
D000700:Analgesics; D004745:Enkephalins; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D011957:Receptors, Opioid; D014862:Wasp Venoms; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D016308:Enkephalin, Leucine-2-Alanine; C037500:mastoparan; D020881:Enkephalin, D-Penicillamine (2,5)-; D019204:GTP-Binding Proteins