Ca2+-dependent PKC activation mediates menthol-induced desensitization of transient receptor potential M8
Ca2+-dependent PKC activation mediates menthol-induced desensitization of transient receptor potential M8
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DOI：
10.1016/j.neulet.2005.12.005
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发表时间：
2006-04-10
影响因子：
2.5
通讯作者：
Kobayashi, S
中科院分区：
文献类型：
--
作者：
Abe, J;Hosokawa, H;Kobayashi, S
在1950年，Hensel和Zotterman通过冷纤维的细胞外放电记录报道了冷受体的冷却诱导的脱敏。然而，从那时起，其细胞内机制仍然没有得到解决。我们研究了薄荷醇诱导的冷/薄荷醇受体（TRPM 8，瞬时受体电位M8）在HEK细胞中表达的脱敏。TRPM 8的脱敏依赖于细胞外Ca 2+离子，表明Ca 2+内流诱导的[Ca 2 +]（i）升高引起了脱敏。我们研究了是否钙依赖性激酶，PKC，介导的TRPM 8脱敏。PMA是一种PKC激活剂，可使TRPM 8脱敏。Ca 2+依赖性PKC同工酶抑制剂特异性地消除PMA诱导的TRPM 8脱敏。PMA类似地使野生型TRPM 8和突变型TRPM 8脱敏，其中一些推定的PKC磷酸化位点中的丝氨酸或苏氨酸残基被丙氨酸取代。PMA处理不诱导TRPM 8的内化。作为冷诱导的冷受体脱敏的基础，我们得出结论，冷激活TRPM 8导致Ca 2+依赖的PKC同工酶对TRPM 8本身脱敏。(C)2005爱思唯尔爱尔兰有限公司保留所有权利。
In 1950, Hensel and Zotterman reported cooling-induced desensitization of cold receptors by extracellular discharge recordings of cold fibers. Since then, however, its intracellular mechanism has remained unresolved. We studied menthol-induced desensitization of cold/menthol receptors (TRPM8, transient receptor potential M8) expressed in HEK cells. TRPM8 desensitization depended on extracellular Ca2+ ions, indicating that Ca2+ influx-induced [Ca2+](i) elevation caused the desensitization. We studied whether Ca2+-dependent kinase, PKC, mediated TRPM8 desensitization. PMA, a PKC activator, desensitized TRPM8. Inhibitor of Ca2+-dependent PKC isozymes specifically abolished PMA-induced TRPM8 desensitization. PMA similarly desensitized wild type TRPM8 and mutant TRPM8, in which serine or threonine residues in some putative PKC phosphorylation sites were replaced by alanine. PMA treatment did not induce internalization of TRPM8. As the basis of cooling-induced desensitization of cold receptors, we conclude that cooling-activated TRPM8 causes Ca2+-dependent PKC isozymes to desensitize TRPM8 itself. (C) 2005 Elsevier Ireland Ltd. All rights reserved.