TRPV3 in keratinocytes transmits temperature information to sensory neurons via ATP.

TRPV3 in keratinocytes transmits temperature information to sensory neurons via ATP.
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DOI:
10.1007/s00424-009-0703-x
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发表时间:
2009-10
期刊:
Pflugers Archiv : European journal of physiology
影响因子:
--
通讯作者:
Tominaga M
Tominaga M
中科院分区:
其他
文献类型:
--
作者:
Mandadi S;Sokabe T;Shibasaki K;Katanosaka K;Mizuno A;Moqrich A;Patapoutian A;Fukumi-Tominaga T;Mizumura K;Tominaga M

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瞬时受体电位V3(TRPV 3)和TRPV 4是角质形成细胞中表达的热激活阳离子通道。已经提出,皮肤中TRPV 3和/或TRPV 4的热激活可以释放可扩散的分子,其然后将激活邻近背根神经节(DRG)神经元的末端。在这里,我们表明,腺苷三磷酸(ATP)是这样一个候选分子释放角质形成细胞加热后,在共培养系统。使用TRPV 1缺陷的DRG神经元,我们发现,只有当神经元与角质形成细胞共培养时,才能观察到加热后DRG神经元胞浆Ca 2+浓度的增加,并且这种增加被P2嘌呤受体拮抗剂PPADS和苏拉明阻断。在角质形成细胞与HEK 293细胞(转染P2 X2 cDNA作为生物传感器)的共培养物中,我们观察到热激活的角质形成细胞分泌ATP,并且TRPV 3缺陷小鼠的角质形成细胞中ATP的释放受到损害。这项研究提供的证据表明,ATP是一种信使分子,主要是TRPV 3介导的皮肤热传导。本文的在线版本(doi:10.1007/s 00424 -009-0703-x)包含补充材料,可供授权用户使用。
Transient receptor potential V3 (TRPV3) and TRPV4 are heat-activated cation channels expressed in keratinocytes. It has been proposed that heat-activation of TRPV3 and/or TRPV4 in the skin may release diffusible molecules which would then activate termini of neighboring dorsal root ganglion (DRG) neurons. Here we show that adenosine triphosphate (ATP) is such a candidate molecule released from keratinocytes upon heating in the co-culture systems. Using TRPV1-deficient DRG neurons, we found that increase in cytosolic Ca2+-concentration in DRG neurons upon heating was observed only when neurons were co-cultured with keratinocytes, and this increase was blocked by P2 purinoreceptor antagonists, PPADS and suramin. In a co-culture of keratinocytes with HEK293 cells (transfected with P2X2 cDNA to serve as a bio-sensor), we observed that heat-activated keratinocytes secretes ATP, and that ATP release is compromised in keratinocytes from TRPV3-deficient mice. This study provides evidence that ATP is a messenger molecule for mainly TRPV3-mediated thermotransduction in skin. The online version of this article (doi:10.1007/s00424-009-0703-x) contains supplementary material, which is available to authorized users.
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