title: Up-regulation of spinal mu-opioid receptor function to activate G-protein by chronic naloxone treatment.
abstract: The effects of repeated s.c. administrations of an mu-opioid receptor antagonist naloxone on the G-protein activation induced by mu-opioid receptor agonists [D-Ala(2),N-MePhe(4),Gly-ol(5)]enkephalin (DAMGO), endomorphin-1 and endomorphin-2 in the mouse spinal cord was studied, monitoring guanosine-5'-o-(3-[35S]thio)triphosphate ([35S]GTPgammaS) binding. All mu-opioid receptor agonists concentration-dependently increased the [35S]GTPgammaS binding. The increases of [35S]GTPgammaS binding induced by agonists were significantly enhanced in mice pretreated with naloxone. Under the present condition, chronic treatment with naloxone significantly increased the density of [3H]DAMGO binding sites with an increase in K(d) values in spinal cord membranes, indicating an increase in mu-opioid receptors on the membrane surface. These findings suggest that chronic treatment with an mu-opioid receptor antagonist naloxone leads to the supersensitivity to activate G-protein by mu-opioid receptor agonists with an increase in mu-opioid receptors in membranes of the mouse spinal cord.
authors.affiliation: Department of Toxicology, School of Pharmacy, Hoshi University, Shinagawa, 142-8501, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Narita
authors.forename: H
authors.initials: H
authors.lastname: Mizoguchi
authors.forename: H
authors.initials: H
authors.lastname: Nagase
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: L F
authors.initials: LF
authors.lastname: Tseng
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000187:drug effects* / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D011869:Radioligand Assay; D017450:Receptors, Opioid, mu / Q000187:drug effects* / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D013462:Sulfur Radioisotopes / Q000493:pharmacokinetics; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; D013462:Sulfur Radioisotopes; C105293:endomorphin 1; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C105294:endomorphin 2; D019204:GTP-Binding Proteins