蛋白激酶Cε参与大鼠背根神经节神经元中TRPV1对辣椒素的基础反应和敏化反应。
Protein kinase C epsilon contributes to basal and sensitizing responses of TRPV1 to capsaicin in rat dorsal root ganglion neurons.
作者信息
Srinivasan Rahul, Wolfe Darren, Goss James, Watkins Simon, de Groat William C, Sculptoreanu Adrian, Glorioso Joseph C
机构信息
Department of Microbiology and Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, PA 15261, USA.
出版信息
Eur J Neurosci. 2008 Oct;28(7):1241-54. doi: 10.1111/j.1460-9568.2008.06438.x.
Abstract
Phosphorylation of the vanilloid receptor (TRPV1) by protein kinase C epsilon (PKCepsilon) plays an important role in the development of chronic pain. Here, we employ a highly defective herpes simplex virus vector (vHDNP) that expresses dominant negative PKCepsilon (DNPKCepsilon) as a strategy to demonstrate that PKCepsilon is essential for: (i) maintenance of basal phosphorylation and normal TRPV1 responses to capsaicin (CAPS), a TRPV1 agonist and (ii) enhancement of TRPV1 responses by phorbol esters. Phorbol esters induced translocation of endogenous PKCepsilon to the plasma membrane and thereby enhanced CAPS currents. These results were extended to an in-vivo pain model in which vHDNP delivery to dorsal root ganglion neurons caused analgesia in CAPS-treated, acutely inflamed rat hind paws. These findings support the conclusion that in addition to receptor sensitization, PKCepsilon is essential for normal TRPV1 responses in vitro and in vivo.
摘要
蛋白激酶Cε（PKCε）对香草酸受体（TRPV1）的磷酸化在慢性疼痛的发展中起重要作用。在此，我们采用一种表达显性负性PKCε（DNPKCε）的高度缺陷型单纯疱疹病毒载体（vHDNP），以证明PKCε对于以下方面至关重要：（i）维持基础磷酸化以及TRPV1对辣椒素（CAPS，一种TRPV1激动剂）的正常反应；（ii）佛波酯增强TRPV1反应。佛波酯诱导内源性PKCε转位至质膜，从而增强CAPS电流。这些结果扩展至体内疼痛模型，其中将vHDNP递送至背根神经节神经元可使经CAPS处理的急性炎症大鼠后爪产生镇痛作用。这些发现支持以下结论：除了受体致敏外，PKCε对于体外和体内正常的TRPV1反应也至关重要。
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