Gx/z and Gi2 transducer proteins on mu/delta opioid-mediated supraspinal antinociception.
Intracerebroventricular (i.c.v.) administration of immune sera raised against Gi2 alpha subunits to mice, significantly reduced the supraspinal antinociceptive effect of opioids when evaluated 24 h later in the tail-flick test. Antisera directed against Gi1 alpha subunits did not modify this opioid activity. In mice injected with sera anti-Gx/z alpha, the mu-preferential agonists, DAMGO and morphine, and the endogenous mu/delta opioid peptide beta-endorphin-(1-31) displayed a reduced antinociceptive activity, whereas, the potency of the delta-selective agonists DPDPE and [D-Ala2]Deltorphin II, was not altered. This reduction was present for 3 to 7 days and returned to the control values after 10 days. Anti-Gi2 alpha and anti-Gx/z alpha, but not anti-Gi1 alpha, reduced the specific binding of [3H]DAMGO to the opioid receptor in PAG. These results suggest the ability of the mu receptor to interact in vivo with different classes of G transducer proteins (Gx/z/Gi2) to produce an effect. This work also indicates a functional role of the pertussis toxin insensitive Gx/z protein, on the mu-mediated (but not delta-mediated) supraspinal antinociception in mice.
Sánchez-Blázquez
P
P
Neurofarmacología, Instituto Cajal, C.S.I.C., Madrid, Spain.
Juarros
J L
JL
Martínez-Peña
Y
Y
Castro
M A
MA
Garzón
J
J
D000595:Amino Acid Sequence; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004745:Enkephalins / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000276:immunology / Q000502:physiology*; D007106:Immune Sera / Q000276:immunology / Q000494:pharmacology; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009292:Narcotic Antagonists / Q000494:pharmacology; D017465:Receptors, Opioid, delta / Q000187:drug effects*; D017450:Receptors, Opioid, mu / Q000187:drug effects*
D000701:Analgesics, Opioid; D004745:Enkephalins; D007106:Immune Sera; D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004743:Enkephalin, Leucine; D020881:Enkephalin, D-Penicillamine (2,5)-; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine; D019204:GTP-Binding Proteins