Regulation of adenosine 5′-triphosphate (ATP)-gated P2X4 receptors on tracheal smooth muscle cells

Miyuki Nagaoka, Masayuki Nara, Tsutomu Tamada, Hiroaki Kume, Tetsuya Oguma, Toshiaki Kikuchi, Jamal Zaini, Takuya Moriya, Masakazu Ichinose, Gen Tamura, Toshio Hattori

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16 Citations (Scopus)

Abstract

We examined the effects of extracellular adenosine 5′-triphosphate (ATP) on single airway smooth muscle (ASM) cells from porcine trachea using a patch-clamp technique. ATP induced a sustained inward current. Phospholipase C inhibitor U-73122 failed to inhibit the current, suggesting the involvement of P2X receptor. A specific effecter of P2X4, ivermectin, augmented the current indicating the existence of P2X4 receptors. Immunohistochemistry and reverse transcription/polymerase chain reaction analysis and Western blot analysis also showed the distribution of the P2X4 receptors. The inward current was reduced by SKF-96365, an inhibitor of both voltage-dependent Ca2+ channels (VDCCs) and voltage-independent Ca2+ channels, although a VDCC antagonist, verapamil, did not affect the current. SKF-96365 caused complete suppression of both the increase in the intracellular Ca2+ concentration and the contraction of ASM cells induced by ATP. Our results demonstrate that P2X4 receptors exist on ASM and that the receptors are responsible for Ca2+ influx. These findings suggest that the Ca2+ influx regulated by P2X4 receptors plays an important role in ASM contraction by a pathway distinct from VDCC.

Original languageEnglish
Pages (from-to)61-67
Number of pages7
JournalRespiratory Physiology and Neurobiology
Volume166
Issue number1
DOIs
Publication statusPublished - 2009 Mar 31

Keywords

  • Airway smooth muscle
  • Ivermectin
  • Purinergic receptor

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology
  • Pulmonary and Respiratory Medicine

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    Nagaoka, M., Nara, M., Tamada, T., Kume, H., Oguma, T., Kikuchi, T., Zaini, J., Moriya, T., Ichinose, M., Tamura, G., & Hattori, T. (2009). Regulation of adenosine 5′-triphosphate (ATP)-gated P2X4 receptors on tracheal smooth muscle cells. Respiratory Physiology and Neurobiology, 166(1), 61-67. https://doi.org/10.1016/j.resp.2009.02.002