ATP Release Mechanisms of Endothelial Cell Mediated Stimulus-Dependent Hyperalgesia

JOURNAL OF PAIN

卷:15

Article

Levine, Jon D.¹ 

[1] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA

关键词: Endothelin-1;    adenosine triphosphate release;    vascular pain;    endothelium;   

DOI  :  10.1016/j.jpain.2014.04.005

来源: Elsevier

【 摘 要 】

Endothelin-1 (ET-1) acts on endothelial cells to enhance mechanical stimulation induced release of adenosine triphosphate (ATP), which in turn can act on sensory neurons innervating blood vessels to contribute to vascular pain, a phenomenon we have referred to as stimulus-dependent hyperalgesia (SDH). In the present study, we evaluated the role of the major classes of ATP release mechanisms to SDH: vesicular exocytosis, plasma membrane associated ATP synthase, ATP-binding cassette transporters, and ion channels. Inhibitors of vesicular exocytosis (ie, monensin, brefeldin A, and bafilomycin), plasma membrane associated ATPase (ie, oligomycin and pigment epithelium derived factor peptide 34-mer), and connexin ion channels (carbenoxolone and flufenamic acid) but not ATP-binding cassette transporter (ie, dipyridamole, nicardipine, or CFTRinh-172) attenuated SDH. This study reports a role of ATP in SDH and suggests novel targets for the treatment of vascular pain syndromes. Perspective: ET-1 acts on endothelial cells to produce mechanical stimulation induced hyperalgesia. Inhibitors of 3 different ATP release mechanisms attenuated this SDH. This study provides support for a role of ATP in SDH and suggests novel targets for the treatment of vascular pain syndromes. (C) 2014 by the American Pain Society

【 授权许可】

Free