1,2-Naphthoquinone activates vanilloid receptor 1 through increased protein tyrosine phosphorylation, leading to contraction of guinea pig trachea

Shota Kikuno, Keiko Taguchi, Noriko Iwamoto, Shigeru Yamano, Arthur K. Cho, John R. Froines, Yoshito Kumagai

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)

Abstract

1,2-Naphthoquinone (1,2-NQ) has recently been identified as an environmental quinone in diesel exhaust particles (DEP) and atmospheric PM 2.5. We have found that this quinone is capable of causing a concentration-dependent contraction of tracheal smooth muscle in guinea pigs with EC50 value of 18.7 μM. The contraction required extracellular calcium and was suppressed by L-type calcium channel blockers nifedipine and diltiazem. It was found that 1,2-NQ activated phospholipase A2 (PLA2)/lipoxygenase (LO)/vanilloid receptor (VR1) signaling. Additionally, 1,2-NQ was capable of transactivating protein tyrosine kinases (PTKs) such as epidermal growth factor receptor (EGFR) in guinea pig trachea, suggesting that phosphorylation of PTKs contributes to 1,2-NQ-induced tracheal contraction. Consistent with this notion, this action was blocked by the PTKs inhibitor genistein and the EGFR antagonist PD153035, indicating that contraction was, at least in part, attributable to PTKs phosphorylation that activates VR1, resulting in increased intracellular calcium content in the smooth muscle cells.

Original languageEnglish
Pages (from-to)47-54
Number of pages8
JournalToxicology and Applied Pharmacology
Volume210
Issue number1-2
DOIs
Publication statusPublished - 2006 Jan

Keywords

  • 1,2-Naphthoquinone
  • Diesel exhaust particles
  • Signal transduction
  • Tracheal contraction
  • Vanilloid (capsaicin) receptor 1

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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