title: Region-dependent G-protein activation by kappa-opioid receptor agonists in the mouse brain.
abstract: The G-protein activations induced by kappa-opioid receptor agonists, (-)U50,488H, U69,593 and TRK-820 in the mouse lower midbrain, striatum and limbic forebrain were determined by monitoring guanosine-5'-o-(3-[35S]thio)triphosphate ([35S]GTP gamma S) binding. All kappa-opioid receptor agonists produced approximately 40, 20 and 10% increases of [35S]GTP gamma S binding over baseline in the lower midbrain, striatum and limbic forebrain, respectively. The increases of [35S]GTP gamma S binding induced by kappa-opioid receptor agonists were completely reversed by the selective kappa-opioid receptor antagonist, norbinaltorphimine (norBNI), in all brain regions. The intrinsic activities of kappa-opioid receptor agonists for G-protein activation in brain regions observed in the present study are not correlated with densities of kappa-opioid receptor binding sites from previous reports. The present results suggest that the catalytic efficiency of kappa-opioid receptor-G-protein coupling may be variable in different brain regions.
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Mizoguchi
authors.forename: Randy J
authors.initials: RJ
authors.lastname: Leitermann
authors.forename: Minoru
authors.initials: M
authors.lastname: Narita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagase
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Suzuki
authors.forename: Leon F
authors.initials: LF
authors.lastname: Tseng
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D000818:Animals; D044482:Benzeneacetamides / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000187:drug effects* / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D009019:Morphinans / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists; D011759:Pyrrolidines / Q000494:pharmacology; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000037:antagonists & inhibitors; D013141:Spiro Compounds / Q000494:pharmacology
chemical_list: D044482:Benzeneacetamides; D009019:Morphinans; D009292:Narcotic Antagonists; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D013141:Spiro Compounds; C111212:TRK 820; C051844:norbinaltorphimine; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D019204:GTP-Binding Proteins; C045444:U 69593