title: G-protein coupling of delta-opioid receptors in brains of mu-opioid receptor knockout mice.
abstract: Mu-opioid receptor knockout mice have been reported to show loss of some delta-opioid receptor function. We hypothesised that this is due to some delta-opioid receptors being uncoupled from G-proteins in the absence of the mu-opioid receptor. To address this possibility, we have used quantitative autoradiography to determine the binding of three delta-opioid receptor agonist ligands ([3H]deltorphin I, [3H] [R-Atc(3), Ile(5,6)]deltorphin II, [3H] 4-[(alpaR)-alpha-((2S,5R)-4-propyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC-121)) and the delta-opioid receptor antagonist, [3H]naltrindole in the presence and absence of a GTP analogue, guanylylimidodiphosphate (GMPPNP) in the brains of mice lacking the mu-opioid receptor gene. Guanylylimidodiphosphate caused a decrease in the binding of the agonist ligands (to differing extents) and an increase in binding for the antagonist in wild-type controls. Overall, there were no major differences in the effects of guanylylimidodiphosphate for the agonist ligands in mu-knockout mice although a few structures showed a smaller sensitivity to the effects of this GTP analogue most notably for [3H]naltrindole. These findings suggest that in the majority of brain regions, G-protein coupling is unaltered in mu-opioid receptor knockout mice.
authors.affiliation: Pharmacology Group, School of Biomedical and Life Sciences, University of Surrey, Surrey GU2 7XH, Guildford, UK.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Oakley
authors.forename: Geza
authors.initials: G
authors.lastname: Toth
authors.forename: Anna
authors.initials: A
authors.lastname: Borsodi
authors.forename: Brigitte L
authors.initials: BL
authors.lastname: Kieffer
authors.forename: Ian
authors.initials: I
authors.lastname: Kitchen
mesh_terms: D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017465:Receptors, Opioid, delta / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000172:deficiency* / Q000235:genetics
chemical_list: D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D006165:Guanylyl Imidodiphosphate; D019204:GTP-Binding Proteins