Small-molecule antagonists of melanopsin-mediated phototransduction.
Small-molecule antagonists of melanopsin-mediated phototransduction.
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DOI：
10.1038/nchembio.1333
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发表时间：
2013-10
影响因子：
14.8
通讯作者：
Panda, Satchidananda
中科院分区：
文献类型：
--
作者：
Jones, Kenneth A.;Hatori, Megumi;Mure, Ludovic S.;Bramley, Jayne R.;Artymyshyn, Roman;Hong, Sang-Phyo;Marzabadi, Mohammad;Zhong, Huailing;Sprouse, Jeffrey;Zhu, Quansheng;Hartwick, Andrew T. E.;Sollars, Patricia J.;Pickard, Gary E.;Panda, Satchidananda
黑视素在视网膜神经节细胞的一个亚群中表达，介导对环境光和其他非成像光反应的行为适应。这提出了一种可能性，即黑视素的药理学操作可以调节几种中枢神经系统反应，包括畏光、睡眠、昼夜节律和神经内分泌功能。在这里，我们描述了一种具有体内活性的强效合成黑视素拮抗剂的鉴定。抑制黑视素的新型磺胺化合物（opsinamide）与视网膜结合黑视素竞争并抑制其功能，而不影响杆/锥介导的反应。在小鼠体内给药opsinamide特异性和可逆地改变了黑视素依赖的光反应，包括瞳孔光反射和光厌恶。opsinamide的发现提高了治疗性控制黑视素光导系统以调节光依赖行为和修复病理条件的前景。
Melanopsin, expressed in a subset of retinal ganglion cells, mediates behavioral adaptation to ambient light and other non-image forming photic responses. This has raised the possibility that pharmacological manipulation of melanopsin can modulate several CNS responses including photophobia, sleep, circadian rhythms and neuroendocrine function. Here we describe the identification of a potent synthetic melanopsin antagonist with in vivo activity. Novel sulfonamide compounds inhibiting melanopsin (opsinamides) compete with retinal binding to melanopsin and inhibit its function without affecting rod/cone mediated responses. In vivo administration of opsinamides to mice specifically and reversibly modified melanopsin-dependent light responses including the pupillary light reflex and light aversion. The discovery of opsinamides raises the prospect of therapeutic control of the melanopsin phototransduction system to regulate light-dependent behavior and remediate pathological conditions.
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影响因子：
33.6
作者：
Do MT;Yau KW
通讯作者：
Yau KW
影响因子：
16.2
作者：
Lall, Gurprit S.;Revell, Victoria L.;Momiji, Hiroshi;Al Enezi, Jazi;Altimus, Cara M.;Gueler, Ali D.;Aguilar, Carlos;Cameron, Morven A.;Allender, Susan;Hankins, Mark W.;Lucas, Robert J.
通讯作者：
Lucas, Robert J.
影响因子：
64.8
作者：
Do, Michael Tri H.;Kang, Shin H.;Xue, Tian;Zhong, Haining;Liao, Hsi-Wen;Bergles, Dwight E.;Yau, King-Wai
通讯作者：
Yau, King-Wai
影响因子：
5.3
作者：
Hartwick, Andrew T. E.;Bramley, Jayne R.;Pickard, Gary E.
通讯作者：
Pickard, Gary E.
影响因子：
64.8
作者：
Melyan, Z;Tarttelin, EE;Hankins, MW
通讯作者：
Hankins, MW