Bhave Gautam, Zhu Weiguo, Wang Haibin, Brasier D J, Oxford Gerry S, Gereau Robert W
Division of Neuroscience, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Neuron. 2002 Aug 15;35(4):721-31. doi: 10.1016/s0896-6273(02)00802-4.
The capsaicin receptor, VR1 (also known as TRPV1), is a ligand-gated ion channel expressed on nociceptive sensory neurons that responds to noxious thermal and chemical stimuli. Capsaicin responses in sensory neurons exhibit robust potentiation by cAMP-dependent protein kinase (PKA). In this study, we demonstrate that PKA reduces VR1 desensitization and directly phosphorylates VR1. In vitro phosphorylation, phosphopeptide mapping, and protein sequencing of VR1 cytoplasmic domains delineate several candidate PKA phosphorylation sites. Electrophysiological analysis of phosphorylation site mutants clearly pinpoints Ser116 as the residue responsible for PKA-dependent modulation of VR1. Given the significant roles of VR1 and PKA in inflammatory pain hypersensitivity, VR1 phosphorylation at Ser116 by PKA may represent an important molecular mechanism involved in the regulation of VR1 function after tissue injury.
辣椒素受体VR1（也称为TRPV1）是一种表达于伤害性感觉神经元上的配体门控离子通道，可对有害的热刺激和化学刺激作出反应。感觉神经元中的辣椒素反应通过cAMP依赖性蛋白激酶（PKA）表现出强烈的增强作用。在本研究中，我们证明PKA可减少VR1脱敏并直接使VR1磷酸化。对VR1胞质结构域进行体外磷酸化、磷酸肽图谱分析和蛋白质测序，确定了几个候选的PKA磷酸化位点。对磷酸化位点突变体的电生理分析明确指出Ser116是负责PKA依赖性调节VR1的残基。鉴于VR1和PKA在炎性疼痛超敏反应中的重要作用，PKA使VR1在Ser116处磷酸化可能代表了一种参与组织损伤后VR1功能调节的重要分子机制。
