Dissimilar efficacy of opioids to produce mu-mediated analgesia: role of Gx/z and Gi2 transducer proteins.
Intracerebroventricular (i.c.v.) administration to mice of IgGs raised against alpha subunits of Gi2 or Gx/z transducer proteins lessened the activation of low Km GTPase induced by morphine, DAMGO and DADLE in P2 membranes from mouse periaqueductal grey matter (PAG). In mice injected with anti Gi2 alpha, DADLE, DPDPE and [D-Ala2] Deltorphin II, but not beta-endorphin-(1-31), antagonized the analgesic activity of morphine. Conversely, following anti Gx/z alpha, morphine antagonized the antinociceptive potency of DADLE. It is concluded that opioids display diverse efficacy at mu-Gi2 and mu-Gx/z complexes to produce supraspinal analgesia in mice.
Garzón
J
J
Instituto Cajal, C.S.I.C., Madrid, Spain.
Martínez-Peña
Y
Y
Sánchez-Blázquez
P
P
D000595:Amino Acid Sequence; D000698:Analgesia; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D004723:Endorphins / Q000494:pharmacology; 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; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000494:pharmacology*; D007276:Injections, Intraventricular; D007700:Kinetics; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology; D010446:Peptide Fragments / Q000276:immunology; D017450:Receptors, Opioid, mu / Q000276:immunology / Q000502:physiology*; D015398:Signal Transduction
D000701:Analgesics, Opioid; D004723:Endorphins; D004745:Enkephalins; D007074:Immunoglobulin G; D010446:Peptide Fragments; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D016308:Enkephalin, Leucine-2-Alanine; D009020:Morphine; D020881:Enkephalin, D-Penicillamine (2,5)-; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins