title: The human histamine H3 receptor couples to GIRK channels in Xenopus oocytes.
abstract: The histamine H(3) receptor mediates inhibitory responses in the nervous system. Here, we demonstrate the coupling of the human histamine H(3) receptor to G protein-coupled inward rectifier potassium (GIRK) channels in Xenopus oocytes, using voltage-clamp. The histamine H(3) receptor agonist (R)-alpha-methylhistamine increased GIRK currents with an EC(50) of 2.5 nM. The response to (R)-alpha-methylhistamine was inhibited by the specific antagonist/inverse agonist clobenpropit. GIRK channels represent a novel effector pathway for the histamine H(3) receptor, also suggesting the use of electrophysiology assays in histamine H(3) receptor drug screening, allowing for the resolution of G protein activation kinetics.
authors.affiliation: Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Sahlholm
authors.forename: Johanna
authors.initials: J
authors.lastname: Nilsson
authors.forename: Daniel
authors.initials: D
authors.lastname: Marcellino
authors.forename: Kjell
authors.initials: K
authors.lastname: Fuxe
authors.forename: Peter
authors.initials: P
authors.lastname: Arhem
mesh_terms: D000818:Animals; D004594:Electrophysiology; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000502:physiology*; D017442:Histamine Agonists / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008761:Methylhistamines / Q000494:pharmacology; D009865:Oocytes / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D018100:Receptors, Histamine H3 / Q000187:drug effects / Q000502:physiology*; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D014981:Xenopus
chemical_list: D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D017442:Histamine Agonists; D006633:Histamine Antagonists; D007093:Imidazoles; D008761:Methylhistamines; D018100:Receptors, Histamine H3; C069357:alpha-methylhistamine; D013890:Thiourea; C086108:clobenpropit