A-kinase anchoring protein mediates TRPV1 thermal hyperalgesia through PKA phosphorylation of TRPV1
A-kinase anchoring protein mediates TRPV1 thermal hyperalgesia through PKA phosphorylation of TRPV1
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DOI：
10.1016/j.pain.2008.02.022
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发表时间：
2008-09-15
期刊：
影响因子：
7.4
通讯作者：
Hargreaves, Kenneth M.
中科院分区：
文献类型：
--
作者：
Jeske, Nathaniel A.;Diogenes, Anibal;Hargreaves, Kenneth M.
某些磷酸化事件受到 A 激酶锚定蛋白 (AKAP) 等支架蛋白的严格控制。油伤害感受末梢、瞬态受体电位通道 1 型 (TRPV1) 磷酸化会导致对许多不同刺激的敏感性。有助于痛觉过敏的发展。在本研究中，我们研究了 AKAP150 在介导 TRPV1 敏化中的功能参与，发现 AKAP150 在大鼠三叉神经节 (TG) 神经元中共表达，并与 TRPV1 相关。此外，siRNA介导的AKAP150表达敲低导致培养的TG神经元中TRPV1的PKA磷酸化显着减少。在 CHO 细胞中，AKAP 上的 PKA RII 结合位点对于 PKA 增强 TRPV1 介导的 Ca2+ 积累是必需的。此外，培养的 TG 神经元中的 AKAP150 敲低减弱了 TRPV1 活性的 PKA 敏化，并且体内施用所有 AKAP 拮抗剂显着降低了前列腺素 E2 对热刺激的敏化。这些数据表明 AKAP150 功能性调节 PKA 介导的 TRPV1 受体磷酸化/敏化。 (C) 2008 年国际疼痛研究协会。由 Elsevier B.V. 出版。保留所有权利。
Certain phosphorylation events are tightly controlled by scaffolding proteins such as A-kinase anchoring protein (AKAP). Oil nociceptive terminals, phosphorylation of transient receptor potential channel type 1 (TRPV1) results ill the sensitization to many different stimuli. contributing to the development of hyperalgesia. In this study, we investigated the functional involvement of AKAP150 in mediating sensitization of TRPV1, and found that AKAP150 is co-expressed in trigeminal ganglia (TG) neurons from rat and associates with TRPV1. Furthermore, siRNA-mediated knock-down of AKAP150 expression led to a significant reduction in PKA phosphorylation of TRPV1 in cultured TG neurons. In CHO cells, the PKA RII binding site on AKAP was necessary for PKA enhancement of TRPV1-mediated Ca2+-accumulation. In addition, AKAP150 knock-down in cultured TG neurons attenuated PKA sensitization of TRPV1 activity and in vivo administration of all AKAP atagonist significantly reduced prostaglandin E2 sensitization to thermal Stimuli. These data suggest that AKAP150 functionally regulates PKA-mediated phosphorylation/sensitization of the TRPV1 receptor. (C) 2008 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.