ATP sensitive potassium channel openers: A new class of ocular hypotensive agents.
ATP sensitive potassium channel openers: A new class of ocular hypotensive agents.
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DOI：
10.1016/j.exer.2016.04.020
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发表时间：
2017-05
影响因子：
3.4
通讯作者：
Fautsch, Michael P.
中科院分区：
文献类型：
--
作者：
Chowdhury, Uttio Roy;Dosa, Peter I.;Fautsch, Michael P.
关键词：
ATP敏感性钾（KATP）通道由于其对ATP和ADP浓度的敏感性而连接细胞的代谢和能量状态。KATP通道已经在身体的多个组织和器官中被鉴定，包括心脏、胰腺、血管平滑肌和骨骼肌。这些通道是专性杂八聚体，含有四个磺酰脲（SUR）和四个钾内向整流（Kir）亚基。基于SUR和Kir的特定类型，存在几种组织特异性KATP通道亚型，每种亚型都有自己独特的功能。最近，KATP通道已被报道在人类和小鼠眼组织。在离体和体内模型系统中，KATP通道开放剂显示出显著的眼部肿胀特性，且没有出现毒副作用。此外，当与已知的眼内压降低药物联合使用时，观察到对IOP降低的累加效应。这些KATP通道开放剂还被报道在缺血应激和谷氨酸诱导的毒性期间保护视网膜神经节细胞，表明该药物类别的神经保护性质。目前用于治疗青光眼等高眼压疾病的药物不能直接保护受影响的视网膜细胞，有时无效，并可能显示出显着的副作用。鉴于此，具有眼水肿和神经保护特性的KATP通道开放剂有可能发展成为一类新的青光眼治疗剂。
ATP sensitive potassium (KATP) channels connect the metabolic and energetic state of cells due to their sensitivity to ATP and ADP concentrations. KATP channels have been identified in multiple tissues and organs of the body including heart, pancreas, vascular smooth muscles and skeletal muscles. These channels are obligatory hetero-octamers and contain four sulfonylurea (SUR) and four potassium inward rectifier (Kir) subunits. Based on the particular type of SUR and Kir present, there are several tissue specific subtypes of KATP channels, each with their own unique set of functions. Recently, KATP channels have been reported in human and mouse ocular tissues. In ex vivo and in vivo model systems, KATP channel openers showed significant ocular hypotensive properties with no appearance of toxic side effects. Additionally, when used in conjunction with known intraocular pressure lowering drugs, an additive effect on IOP reduction was observed. These KATP channel openers have also been reported to protect the retinal ganglion cells during ischemic stress and glutamate induced toxicity suggesting a neuroprotective property for this drug class. Medications that are currently used for treating ocular hypertensive diseases like glaucoma do not directly protect the affected retinal cells, are sometimes ineffective and may show significant side effects. In light of this, KATP channel openers with both ocular hypotensive and neuroprotective properties, have the potential to develop into a new class of glaucoma therapeutics.
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影响因子：
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作者：
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