Toxicology and applied pharmacology, 2006-01, Vol.210 (1), p.47-54
2006
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- Autor(en) / Beteiligte
- Titel
- 1,2-Naphthoquinone activates vanilloid receptor 1 through increased protein tyrosine phosphorylation, leading to contraction of guinea pig trachea
- Ist Teil von
- Toxicology and applied pharmacology, 2006-01, Vol.210 (1), p.47-54
- Ort / Verlag
- San Diego, CA: Elsevier Inc
- Erscheinungsjahr
- 2006
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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 EC 50 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0041-008XeISSN: 1096-0333DOI: 10.1016/j.taap.2005.06.015Titel-ID: cdi_osti_scitechconnect_20783399
- Format
- –
- Schlagworte
- 1,2-Naphthoquinone, 60 APPLIED LIFE SCIENCES, Air Pollutants - toxicity, Animals, BENZOQUINONES, Biological and medical sciences, BRADYKININ, CALCIUM, Calcium Channels, L-Type - metabolism, Diesel exhaust particles, Dose-Response Relationship, Drug, ELECTROPHORESIS, GELS, GLUTATHIONE, GROWTH FACTORS, GUINEA PIGS, In Vitro Techniques, LEAD SULFIDES, Lipoxygenase - metabolism, Male, MASS SPECTROSCOPY, Medical sciences, Muscle Contraction - drug effects, Muscle, Smooth - drug effects, Muscle, Smooth - enzymology, Muscle, Smooth - metabolism, MUSCLES, Naphthoquinones - toxicity, NUCLEAR MAGNETIC RESONANCE, OXYGEN, PHOSPHATES, Phospholipases A - metabolism, Phospholipases A2, PHOSPHORYLATION, PHOSPHOTRANSFERASES, Protein-Tyrosine Kinases - metabolism, RECEPTORS, Signal transduction, Signal Transduction - drug effects, Toxicology, TRACHEA, Trachea - drug effects, Trachea - enzymology, Trachea - metabolism, Tracheal contraction, TRPV Cation Channels - antagonists & inhibitors, TRPV Cation Channels - metabolism, TYROSINE, Vanilloid (capsaicin) receptor 1