HTR7 Mediates Serotonergic Acute and Chronic Itch.
HTR7 Mediates Serotonergic Acute and Chronic Itch.
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HTR7 介导血清素能急性和慢性瘙痒
DOI：
10.1016/j.neuron.2015.05.044
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发表时间：
2015-07-01
期刊：
影响因子：
16.2
通讯作者：
Bautista DM
中科院分区：
文献类型：
--
作者：
Morita T;McClain SP;Batia LM;Pellegrino M;Wilson SR;Kienzler MA;Lyman K;Olsen AS;Wong JF;Stucky CL;Brem RB;Bautista DM
慢性瘙痒是一种流行的、使人虚弱的疾病，几乎没有有效的治疗方法。我们利用遗传上不同的小鼠品系之间的自然变异来识别与瘙痒行为共同调节的转录本。这项调查导致了5-羟色胺受体HTR7的发现，它是5-羟色胺能瘙痒的关键媒介。HTR7的激活促进了离子通道TRPA1的开放，进而触发了瘙痒行为。此外，由5-羟色胺或选择性5-羟色胺再摄取抑制剂引发的急性瘙痒需要HTR7和TRPA1。长期以来，5-羟色胺信号的异常与各种人类慢性瘙痒疾病有关，包括特应性皮炎。在特应性皮炎的小鼠模型中，缺乏HTR7或TRPA1的小鼠表现出较少的抓挠和皮肤损伤严重程度。这些数据强调了HTR7在急性和慢性瘙痒中的作用，并表明HTR7拮抗剂可能对治疗各种病理性瘙痒状况有用。
Chronic itch is a prevalent and debilitating condition for which few effective therapies are available. We harnessed the natural variation across genetically distinct mouse strains to identify transcripts co-regulated with itch behavior. This survey led to the discovery of the serotonin receptor, HTR7, as a key mediator of serotonergic itch. Activation of HTR7 promoted opening of the ion channel TRPA1, which in turn triggered itch behaviors. In addition, acute itch triggered by serotonin or a selective serotonin reuptake inhibitor required both HTR7 and TRPA1. Aberrant serotonin signaling has long been linked to a variety of human chronic itch conditions, including atopic dermatitis. In a mouse model of atopic dermatitis, mice lacking HTR7 or TRPA1 displayed reduced scratching and skin lesion severity. These data highlight a role for HTR7 in acute and chronic itch, and suggest that HTR7 antagonists may be useful for treating a variety of pathological itch conditions.