CFTR mediates noradrenaline-induced ATP efflux from DRG neurons

Molecular Pain

Tomoyuki Nishizaki¹  Takeshi Kanno¹ 

[1] Division of Bioinformation, Department of Physiology, Hyogo College of Medicine 1-1 Mukogawa-cho, Nishinomiya, 663-8501, Japan

关键词: cystic fibrosis transmembrane conductance regulator;    ATP efflux;    neuron;    Dorsal root ganglion;    Noradrenaline;   

Others  :  865745
DOI  :  10.1186/1744-8069-7-72

 received in 2011-08-11, accepted in 2011-09-24,  发布年份 2011

【 摘 要 】

In our earlier study, noradrenaline (NA) stimulated ATP release from dorsal root ganglion (DRG) neurons as mediated via β₃ adrenoceptors linked to G_s protein involving protein kinase A (PKA) activation, to cause allodynia. The present study was conducted to understand how ATP is released from DRG neurons. In an outside-out patch-clamp configuration from acutely dissociated rat DRG neurons, single-channel currents, sensitive to the P2X receptor inhibitor PPADS, were evoked by approaching the patch-electrode tip close to a neuron, indicating that ATP is released from DRG neurons, to activate P2X receptor. NA increased the frequency of the single-channel events, but such NA effect was not found for DRG neurons transfected with the siRNA to silence the cystic fibrosis transmembrane conductance regulator (CFTR) gene. In the immunocytochemical study using acutely dissociated rat DRG cells, CFTR was expressed in neurons alone, but not satellite cells, fibroblasts, or Schwann cells. It is concluded from these results that CFTR mediates NA-induced ATP efflux from DRG neurons as an ATP channel.

【 授权许可】

   
2011 Kanno and Nishizaki; licensee BioMed Central Ltd.

【 图 表 】

【 参考文献 】

• [1]Burnstock G: Purinergic P2 receptors as targets for novel analgesics. Pharmacol Ther 2006, 110:433-454.
• [2]Burnstock G: Purinergic receptors and pain. Curr Pharm Des 2009, 15:1717-1735.
• [3]Chen CC, Akopian AN, Sivilotti L, Colquhoun D, Burnstock G, Wood JN: A P2X purinoceptor expressed by a subset of sensory neurons. Nature 1995, 377:428-431.
• [4]Hamilton SG, McMahon SB: ATP as a peripheral mediators of pain. J Auton Nerv Syst 2000, 81:187-194.
• [5]Lewis C, Neidhart S, Holy C, North RA, Buell G, Surprenant A: Coexpression of P2X2 and P2X3 receptor subunits can account for ATP-gated currents in sensory neurons. Nature 1995, 377:432-435.
• [6]Moriyama T, Iida T, Kobayashi K, Higashi T, Fukuoka T, Tsumura H, Leon C, Suzuki N, Inoue K, Gachet C, Noguchi K, Tominaga M: Possible involvement of P2Y2 metabotropic receptors in ATP-induced transient receptor potential vanilloid receptor 1-mediated thermal hypersensitivity. J Neurosci 2003, 23:6058-6062.
• [7]North RA: P2X3 receptor and peripheral pain mechanisms. J Physiol 2004, 554:301-308.
• [8]Tsuda M, Shigemoto-Mogami Y, Ueno S, Koizumi S, Ueda H, Iwanaga T, Inoue K: Downregulation of P2X3 receptor-dependent sensory functions in A/J inbred mouse strain. Eur J Neurosci 2002, 15:1444-1450.
• [9]Vlaskovska M, Kasakov L, Rong W, Bodin P, Bardini M, Cockayne DA, Ford AP, Burnstock G: P2X3 knock-out mice reveal a major sensory role for urothelially released ATP. J Neurosci 2001, 21:5670-5677.
• [10]Mclachlan EM, Janig W, Devor M, Michaelis M: Peripheral nerve injury triggers noradrenergic sprouting within dorsal root ganglia. Nature 1993, 363:543-546.
• [11]Kim HJ, Na HS, Back SK, Hong SK: Sympathetic sprouting in sensory ganglia depends on the number of injured neurons. NeuroReport 2001, 12:3529-3532.
• [12]Chung JM, Chung K: Importance of hyperexcitability of DRG neurons in neuropathic pain. Pain Pract 2002, 2:87-97.
• [13]Maruo K, Yamamoto H, Yamamoto S, Nagata T, Fujikawa H, Kanno T, Yaguchi T, Maruo S, Yoshiya S, Nishizaki T: Modulation of P2X receptors via adrenergic pathways in rat dorsal root ganglion neurons after sciatic nerve injury. Pain 2006, 120:106-112.
• [14]Kanno T, Yaguchi T, Nishizaki T: Noradrenaline stimulates ATP release from DRG neurons by targeting β3 adrenoceptors as a factor of neuropathic pain. J Cell Physiol 2010, 224:345-351.
• [15]Reisin IL, Prat AG, Abraham EH, Amara JF, Gregory RJ, Ausiello DA, Cantiello HF: The cystic fibrosis transmembrane conductance regulator is a dual ATP and chloride channel. J Biol Chem 1994, 269:20584-20591.
• [16]Marcet B, Boeynaems JM: Relationships between cystic fibrosis transmembrane conductance regulator, extracellular nucleotides and cystic fibrosis. Pharmacol Ther 2006, 112:719-732.
• [17]Picciotto MR, Cohn JA, Bertuzzi G, Greengard P, Nairn AC: Phosphorylation of the cystic fibrosis transmembrane conductance regulator. J Biol Chem 1992, 267:12742-12752.
• [18]Berger HA, Travis SM, Welsh MJ: Regulation of the cystic fibrosis transmembrane conductance regulator Cl- channel by specific protein kinases and protein phosphatases. J Biol Chem 1993, 268:2037-2047.