The human histamine H3 receptor couples to GIRK channels in Xenopus oocytes.
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.
Sahlholm
Kristoffer
K
Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
Nilsson
Johanna
J
Marcellino
Daniel
D
Fuxe
Kjell
K
Arhem
Peter
P
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
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