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
收藏
页码：494 / 500
页数：7
相关论文
共 45 条
  • [1] Activation of 5-HT2A receptors potentiates pain produced by inflammatory mediators
    Abbott, FV
    Hong, Y
    Blier, P
    [J]. NEUROPHARMACOLOGY, 1996, 35 (01) : 99 - 110
  • [2] Persisting sensitization of the behavioural response to formalin-induced injury in the rat through activation of serotonin(2A) receptors
    Abbott, FV
    Hong, Y
    Blier, P
    [J]. NEUROSCIENCE, 1997, 77 (02) : 575 - 584
  • [3] Protein kinase C stimulates the acid-sensing ion channel ASIC2a via the PDZ domain-containing protein PICK1
    Baron, A
    Deval, E
    Salinas, M
    Lingueglia, E
    Voilley, N
    Lazdunski, M
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (52) : 50463 - 50468
  • [4] Modulation of acid-sensing ion channel activity by nitric oxide
    Cadiou, Herve
    Studer, Milena
    Jones, Nicholas G.
    Smith, Ewan St. J.
    Ballard, Angela
    McMahon, Stephen B.
    McNaughton, Peter A.
    [J]. JOURNAL OF NEUROSCIENCE, 2007, 27 (48) : 13251 - 13260
  • [5] Chen JJ, 1998, J PHARMACOL EXP THER, V287, P1119
  • [6] Strong modulation by RFamide neuropeptides of the ASIClb/3 heteromer in competition with extracellular calcium
    Chen, Xuanmao
    Paukert, Martin
    Kadurin, Ivan
    Pusch, Michael
    Gruender, Stefan
    [J]. NEUROPHARMACOLOGY, 2006, 50 (08) : 964 - 974
  • [7] Functional implications of the localization and activity of acid-sensitive channels in rat peripheral nervous system
    de la Rosa, DA
    Zhang, P
    Shao, D
    White, F
    Canessa, CM
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (04) : 2326 - 2331
  • [8] ASIC2b-dependent regulation of ASIC3, an essential acid-sensing ion channel subunit in sensory neurons via the partner protein PICK-1
    Deval, E
    Salinas, M
    Baron, A
    Lingueglia, E
    Lazdunski, M
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (19) : 19531 - 19539
  • [9] ASIC3, a sensor of acidic and primary inflammatory pain
    Deval, Emmanuel
    Noel, Jacques
    Lay, Nadege
    Alloui, Abdelkrim
    Diochot, Sylvie
    Friend, Valerie
    Jodar, Martine
    Lazdunski, Michel
    Lingueglia, Eric
    [J]. EMBO JOURNAL, 2008, 27 (22) : 3047 - 3055
  • [10] Acid-Sensing Ion Channels in Postoperative Pain
    Deval, Emmanuel
    Noel, Jacques
    Gasull, Xavier
    Delaunay, Anne
    Alloui, Abdelkrim
    Friend, Valerie
    Eschalier, Alain
    Lazdunski, Michel
    Lingueglia, Eric
    [J]. JOURNAL OF NEUROSCIENCE, 2011, 31 (16) : 6059 - 6066
12345