γ-氨基丁酸受体
组胺
配体门控离子通道
甘氨酸受体
γ-氨基丁酸受体
半胱氨酸环受体
离子通道
组胺H1受体
组胺受体
生物
神经科学
氯离子通道
受体
组胺能
抑制性突触后电位
苦毒毒素
化学
药理学
细胞生物学
生物化学
氨基酸
甘氨酸
敌手
烟碱激动剂
烟碱乙酰胆碱受体
作者
Mark W. Fleck,Jeffrey L. Thomson,Lindsay B. Hough
标识
DOI:10.1016/j.bcp.2011.12.011
摘要
There is ample pharmacological and physiological evidence for yet unidentified histamine receptors in mammalian brain that are linked to a Cl− conductance. In invertebrates, two histamine-gated chloride channels (HisCl α1 and α2) are already well known. HisCl channels are members of the Cys-loop receptor superfamily of ligand-gated ion channels and are closely related to the mammalian GABAA and glycine receptors (GlyR). Indeed, they share particularly strong homology within the ligand binding and ion channel domains. Here we discuss the possibility that mammalian HisCl channels might exist among the known GABAA or GlyR subunits. Studies published to date support this hypothesis, including evidence for direct histamine gating of GABAA β homomers, histamine potentiation of GABAA αβ and αβγ heteromeric receptors, and GABAA receptor blockade by some antihistamines. We explore what is known about the binding-site structure, function and pharmacology of invertebrate HisCl channels and other histamine binding sites to support and inform a broader search for HisCl channels among the mammalian GABAA and GlyR subunits. The discovery and identification of HisCl-like channels in mammals would not only enhance understanding of inhibitory signaling and histamine function in the mammalian brain, but also provide new avenues for development of therapeutic compounds targeting this novel histamine site. This commentary is therefore intended to foster consideration of a novel and potentially important target of histamine and histaminergic drugs in the CNS.
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