A capsaicin-receptor homologue with a high threshold for noxious heat
A capsaicin-receptor homologue with a high threshold for noxious heat
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DOI：
10.1038/18906
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发表时间：
1999-04-01
期刊：
影响因子：
64.8
通讯作者：
Julius, D
中科院分区：
文献类型：
--
作者：
Caterina, MJ;Rosen, TA;Julius, D
产生疼痛的热量由几类伤害性感觉神经元检测，这些神经元的热反应阈值不同（1-3）。克隆的辣椒素受体，也称为香草素受体亚型1（VR 1），是一种热门控离子通道，已被提出介导小直径感觉神经元对中等（43 ℃）热刺激的反应（4，5）。VR 1也被质子激活，表明它可能参与体内有害热和化学刺激的检测。在这里，我们确定了一个结构相关的受体，VRL-1，不响应辣椒素，酸或中度热。相反，VRL-1是由高温激活的，其阈值类似于52摄氏度。在感觉神经节内，VRL-1最显著地由中等至大直径神经元的子集表达，使其成为在这类细胞中转导高阈值热反应的候选受体。VRL-1转录本并不局限于感觉神经系统，这表明该通道可能被热以外的刺激激活。我们认为，对有毒热的反应涉及这些相关但不同的离子通道亚型，它们共同检测一系列刺激强度。
Pain-producing heat is detected by several classes of nociceptive sensory neuron that differ in their thermal response thresholds(1-3). The cloned capsaicin receptor, also known as the vanilloid receptor subtype 1 (VR1), is a heat-gated ion channel that has been proposed to mediate responses of small-diameter sensory neurons to moderate (43 degrees C) thermal stimuli(4,5). VR1 is also activated by protons, indicating that it may participate in the detection of noxious thermal and chemical stimuli in vivo. Here we identify a structurally related receptor, VRL-1, that does not respond to capsaicin, acid or moderate heat. Instead, VRL-1 is activated by high temperatures, with a threshold of similar to 52 degrees C. Within sensory ganglia, VRL-1 is most prominently expressed by a subset of medium- to large-diameter neurons, making it a candidate receptor for transducing high-threshold heat responses in this dass of cells. VRL-1 transcripts are not restricted to the sensory nervous system, indicating that this channel may be activated by stimuli other than heat. We propose that responses to noxious heat involve these related, but distinct, ion-channel subtypes that together detect a range of stimulus intensities.