Trpm5 null mice respond to bitter, sweet, and umami compounds
Trpm5 null mice respond to bitter, sweet, and umami compounds
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DOI：
10.1093/chemse/bjj027
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发表时间：
2006-03-01
期刊：
影响因子：
3.5
通讯作者：
Margolskee, RF
中科院分区：
文献类型：
--
作者：
Damak, S;Rong, MQ;Margolskee, RF
Trpm5是一种在味觉受体细胞中选择性表达的钙激活阳离子通道。先前的一项研究报道，内部缺失Trpm5的小鼠，缺乏编码跨膜段1-5的外显子15-19，对苦、甜和鲜味化合物没有味觉介导的反应。由于Trpm5的启动子区域和外显子1-4（包括翻译起始位点）的缺失，我们独立生成了Trpm5蛋白表达缺失的敲除小鼠。我们通过三种方法检测了Trpm5缺失小鼠和野生型（WT）小鼠的味觉介导反应：味觉神经记录[耳廓索（CT）和舌咽部（NG）神经]、初始舔反应和24小时两瓶偏好测试。对于苦味化合物，Trpm5缺失小鼠表现出减少，但不是完全消除的回避行为（舔食反应和偏好比高于WT），正常的CT反应，以及大大减少的NG反应。对于甜味化合物，Trpm5缺失小鼠没有舔食反应，偏好比降低，神经反应缺失或大大减少。对于鲜味化合物，Trpm5缺失小鼠没有舔食反应，偏好比降低，NG反应正常，CT反应大大降低。我们的研究结果表明，消除Trmp5表达的后果取决于所检查的味觉质量和舌味觉领域。因此，虽然Trpm5在许多味觉反应中是一个重要因素，但它的缺失并不能消除所有的味觉反应。我们得出结论，trpm5依赖性和trpm5非依赖性通路是苦味、甜味和鲜味的基础。
Trpm5 is a calcium-activated cation channel expressed selectively in taste receptor cells. A previous study reported that mice with an internal deletion of Trpm5, lacking exons 15-19 encoding transmembrane segments 1-5, showed no taste-mediated responses to bitter, sweet, and umami compounds. We independently generated knockout mice null for Trpm5 protein expression due to deletion of Trpm5's promoter region and exons 1-4 (including the translation start site). We examined the taste-mediated responses of Trpm5 null mice and wild-type (WT) mice using three procedures: gustatory nerve recording [chorda tympani (CT) and glossopharyngeal (NG) nerves], initial lick responses, and 24-h two-bottle preference tests. With bitter compounds, the Trpm5 null mice showed reduced, but not abolished, avoidance (as indicated by licking responses and preference ratios higher than those of WT), a normal CT response, and a greatly diminished NG response. With sweet compounds, Trpm5 null mice showed no licking response, a diminished preference ratio, and absent or greatly reduced nerve responses. With umami compounds, Trpm5 null mice showed no licking response, a diminished preference ratio, a normal NG response, and a greatly diminished CT response. Our results demonstrate that the consequences of eliminating Trmp5 expression vary depending upon the taste quality and the lingual taste field examined. Thus, while Trpm5 is an important factor in many taste responses, its absence does not eliminate all taste responses. We conclude that Trpm5-dependent and Trpm5-independent pathways underlie bitter, sweet, and umami tastes.