title: 1,2-Naphthoquinone activates vanilloid receptor 1 through increased protein tyrosine phosphorylation, leading to contraction of guinea pig trachea.
abstract: 1,2-Naphthoquinone (1,2-NQ) has recently been identified as an environmental quinone in diesel exhaust particles (DEP) and atmospheric PM2.5. 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 microM. 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.
authors.affiliation: Master's Program in Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Shota
authors.initials: S
authors.lastname: Kikuno
authors.forename: Keiko
authors.initials: K
authors.lastname: Taguchi
authors.forename: Noriko
authors.initials: N
authors.lastname: Iwamoto
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yamano
authors.forename: Arthur K
authors.initials: AK
authors.lastname: Cho
authors.forename: John R
authors.initials: JR
authors.lastname: Froines
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Kumagai
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008084:Lipoxygenase / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009285:Naphthoquinones / Q000633:toxicity*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014132:Trachea / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism
chemical_list: D000393:Air Pollutants; D020746:Calcium Channels, L-Type; D009285:Naphthoquinones; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; C040756:1,2-naphthoquinone; D008084:Lipoxygenase; D011505:Protein-Tyrosine Kinases; D010741:Phospholipases A; D054467:Phospholipases A2