Impairment of Bitter Taste Sensor Transient Receptor Potential Channel M5-Mediated Aversion Aggravates High-Salt Intake and Hypertension
Impairment of Bitter Taste Sensor Transient Receptor Potential Channel M5-Mediated Aversion Aggravates High-Salt Intake and Hypertension
复制标题
苦味传感器瞬时受体电位通道 M5 介导的厌恶感受损加剧高盐摄入和高血压
DOI：
10.1161/hypertensionaha.119.13358
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发表时间：
2019-10-01
期刊：
影响因子：
8.3
通讯作者：
Zhu, Zhiming
中科院分区：
文献类型：
--
作者：
Cui, Yuanting;Wu, Hao;Zhu, Zhiming
过量的盐摄入会导致心血管疾病。尽管采取了各种旨在减少盐摄入量的措施，但每日盐摄入量仍然很高。适量的盐摄入是通过上皮钠通道诱发的盐味偏好和苦味感受器瞬时受体电位通道M5（TRPM 5）诱发的盐味厌恶来平衡的。然而，过量盐摄入的行为机制在很大程度上仍然难以捉摸。本研究以野生型和TRPM 5（-/-）小鼠为研究对象，研究高盐对上皮钠通道/TRPM 5的影响及其对盐消耗行为的影响。我们发现，长期高盐摄入会削弱小鼠对高盐刺激的厌恶行为，但不会改变小鼠对低盐的偏好。机制证据表明，高盐摄入通过抑制舌上皮细胞中蛋白激酶C（PKC）活性和PKC依赖的苏氨酸磷酸化来减弱TRPM 5介导的对有害盐刺激的厌恶行为，但不影响上皮细胞钠通道依赖的盐味觉偏好。TRPM 5的抑制也导致对高盐的厌恶反应受损，小鼠苦味皮质区的味觉感知降低。TRPM 5（-/-）小鼠表现出对高盐饮食的厌恶程度降低，并出现盐诱导的高血压。高盐摄入的高血压患者对高盐摄入引起的苦味感知障碍也存在。我们证明，长期高盐消费损害厌恶反应，浓盐通过下调苦味传感器TRPM 5。提示增强TRPM 5功能可能对抗高盐摄入和高盐性高血压。
Excessive salt consumption leads to cardiovascular diseases. Despite various measures designed to reduce salt intake, daily salt intake remains at a high level. Appropriate salt intake is balanced by salt taste preference triggered by epithelium sodium channel and salt taste aversion evoked by bitter taste sensor, transient receptor potential channel M5 (TRPM5). However, the behavioral mechanism of excessive salt intake remains largely elusive. In this study, wild type and TRPM5(-/-) mice were applied to study the influence of high-salt administration on epithelium sodium channel/TRPM5 and the associated behavior to salt consumption. We found that long-term high-salt intake impaired the aversive behavior to high-salt stimulation but did not alter the preference to low salt in mice. The mechanistic evidence demonstrated that high-salt intake blunted the TRPM5-mediated aversive behavior to noxious salt stimulation through inhibiting PKC (protein kinase C) activity and PKC-dependent threonine phosphorylation in the tongue epithelium but did not affect the epithelium sodium channel-dependent salt taste preference. Inhibition of TRPM5 also resulted in an impaired aversive response to high salt, with reduced taste perception in bitter cortical field of mice. TRPM5(-/-) mice showed a lowered aversion to high-salt diet and developed salt-induced hypertension. The impaired perception to bitter taste evoked by high-salt intake also existed in hypertensive patients with high-salt consumption. We demonstrate that long-term high-salt consumption impairs aversive response to concentrated salt by downregulating bitter taste sensor TRPM5. It suggests that enhancing TRPM5 function might antagonize excessive salt intake and high salt-induced hypertension.