Adenosine and the auditory system.
Adenosine and the auditory system.
复制标题
腺苷和听觉系统。
DOI：
10.2174/157015909789152155
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发表时间：
2009-09
影响因子：
5.3
通讯作者：
Thorne PR
中科院分区：
文献类型：
--
作者：
Vlajkovic SM;Housley GD;Thorne PR
腺苷是一种信号分子，通过四种G蛋白偶联受体A1、A2 A、A2 B和A3调节中枢神经系统和外周器官的细胞活性。本文综述了腺苷在听觉功能中的作用，特别是耳蜗功能及其对氧化应激的保护作用。腺苷受体在哺乳动物耳蜗中的特定组织分布暗示腺苷信号传导在感觉传导和听觉神经传递中，尽管功能研究已经证明腺苷刺激耳蜗血流，但不改变静息和声音诱发的听觉电位。腺苷的潜在耳保护作用的兴趣最近已经发展，由A1腺苷受体的能力，以防止耳蜗损伤所造成的声创伤和耳毒性药物的燃料。A1和A2 A受体之间的平衡被认为是耳蜗对氧化应激反应的关键，氧化应激是最常见的内耳病理学（例如噪声诱导的和年龄相关的听力损失，药物耳毒性）的潜在机制。参与腺苷代谢的酶，腺苷激酶和腺苷脱氨酶，也成为控制耳蜗氧化应激的有吸引力的靶点。其他可能的靶点包括从细胞外ATP产生腺苷的胞外核苷酸酶，以及调节质膜两侧腺苷浓度的核苷转运蛋白。能够穿过血-耳蜗屏障的选择性腺苷受体激动剂和拮抗剂的开发正在支持开发旨在改善耳蜗损伤的治疗干预措施的努力。因此，腺苷信号系统的操纵在耳蜗氧化应激的治疗管理中具有重要的前景。
Adenosine is a signalling molecule that modulates cellular activity in the central nervous system and peripheral organs via four G protein-coupled receptors designated A1, A2A, A2B, and A3. This review surveys the literature on the role of adenosine in auditory function, particularly cochlear function and its protection from oxidative stress. The specific tissue distribution of adenosine receptors in the mammalian cochlea implicates adenosine signalling in sensory transduction and auditory neurotransmission although functional studies have demonstrated that adenosine stimulates cochlear blood flow, but does not alter the resting and sound-evoked auditory potentials. An interest in a potential otoprotective role for adenosine has recently evolved, fuelled by the capacity of A1 adenosine receptors to prevent cochlear injury caused by acoustic trauma and ototoxic drugs. The balance between A1 and A2A receptors is conceived as critical for cochlear response to oxidative stress, which is an underlying mechanism of the most common inner ear pathologies (e.g. noise-induced and age-related hearing loss, drug ototoxicity). Enzymes involved in adenosine metabolism, adenosine kinase and adenosine deaminase, are also emerging as attractive targets for controlling oxidative stress in the cochlea. Other possible targets include ectonucleotidases that generate adenosine from extracellular ATP, and nucleoside transporters, which regulate adenosine concentrations on both sides of the plasma membrane. Developments of selective adenosine receptor agonists and antagonists that can cross the blood-cochlea barrier are bolstering efforts to develop therapeutic interventions aimed at ameliorating cochlear injury. Manipulations of the adenosine signalling system thus hold significant promise in the therapeutic management of oxidative stress in the cochlea.
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