Sahlholm Kristoffer, Nilsson Johanna, Marcellino Daniel, Fuxe Kjell, Arhem Peter
Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
Eur J Pharmacol. 2007 Jul 19;567(3):206-10. doi: 10.1016/j.ejphar.2007.04.032. Epub 2007 Apr 30.
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.
组胺H(3)受体介导神经系统中的抑制性反应。在此，我们利用电压钳技术，在非洲爪蟾卵母细胞中证明了人类组胺H(3)受体与G蛋白偶联内向整流钾通道（GIRK）的偶联。组胺H(3)受体激动剂（R）-α-甲基组胺以2.5 nM的半数有效浓度（EC(50)）增加GIRK电流。对（R）-α-甲基组胺的反应被特异性拮抗剂/反向激动剂氯苯丙哌嗪抑制。GIRK通道代表了组胺H(3)受体的一种新的效应途径，这也表明在组胺H(3)受体药物筛选中可使用电生理测定法，从而解析G蛋白激活动力学。
