Potentiation of acid-sensing ion channel activity by the activation of 5-HT2 receptors in rat dorsal root ganglion neurons

被引：33

作者：

Qiu, Fang ^{[1
]}

Qiu, Chun-Yu

Liu, Yu-Qiang

Wu, Dan

Li, Jia-Da ^{[2
]}

Hu, Wang-Ping ^{[1
]}

机构：

[1] Hubei Univ Sci & Technol, Lab Cardiovasc Cerebrovasc & Metab Disorder, Dept Pharmacol, Xianning 437100, Hubei, Peoples R China

[2] Cent S Univ, State Key Lab Med Genet, Changsha 410078, Hunan, Peoples R China

来源：

NEUROPHARMACOLOGY | 2012年 / 63卷 / 03期

基金：

中国国家自然科学基金;

关键词：

Acid-sensing ion channel; 5-HT2; receptor; Proton-gated current; Neuronal excitability; Dorsal root ganglion neuron; BRAIN NA+ CHANNEL; PROTEIN-KINASE-C; SENSORY NEURONS; INFLAMMATORY MEDIATORS; PAIN; SEROTONIN; SENSITIZATION; NOCICEPTORS; MODULATION; EXPRESSION;

D O I：

10.1016/j.neuropharm.2012.04.034

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Acid-sensing ion channels (ASICs), as key sensors for extracellular protons, are expressed in nociceptive sensory neurons and contribute to signalling pain caused by tissue acidosis. ASICs are also the subject of various factors. Here, we further provide evidence that the activity of ASICs is potentiated by the activation of 5-HT2 receptors in rat dorsal root ganglion neurons. A specific 5-HT2 receptor agonist, alpha-methyl-5-HT, dose-dependently enhanced proton-gated currents with an EC50 of 0.13 +/- 0.07 nM. The alpha-methyl-5-HT enhancing effect on proton-gated currents was blocked by cyproheptadine, a 5-HT2 receptor antagonist, and removed by intracellular dialysis of either GDP-beta-S or protein kinase C inhibitor GF109203X. Moreover, alpha-methyl-5-HT altered acid-evoked membrane excitability of rat DRG neurons and caused a significant increase in the amplitude of the depolarization and the number of spikes induced by acid stimuli. Finally, alpha-methyl-5-HT increased nociceptive responses to injection of acetic acid in rats. These results suggest that alpha-methyl-5-HT up-regulates the activity of ASICs via 5-HT2 receptor and protein kinase C dependent signal pathways in rat primary sensory neurons and this potentiation contributed to acid- mediated pain in tissue injury and inflammation. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：494 / 500

页数：7

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