Enhanced airway smooth muscle cell thromboxane receptor signaling via activation of JNK MAPK and extracellular calcium influx

Ying Lei, Yongxiao Cao, Yaping Zhang, Lars Edvinsson, Cang-Bao Xu

15 Citationer (Scopus)

Abstrakt

Thromboxane is a key inflammatory mediator and potent airway constrictor. It acts on thromboxane A(2) (TP) receptors and contributes to airway inflammation and airway hyperresponsiveness that is the characteristic feature of asthma. The present study was designed to study TP receptor signaling in airway smooth muscle cells by using an organ culture model and a set of selective pharmacological inhibitors for mitogen-activated protein kinase (MAPK) and calcium signal pathways. Western-blot, immunohistochemistry, myograph and a selective TP receptor agonist U46619 were used for examining TP receptor signal proteins and function. Organ culture of rat bronchial segments for up to 48 h induces a time-dependently increased airway contractile response to U46619. This indicates that organ culture increases TP receptor signaling in the airway smooth muscle cells. The enhanced bronchial contraction was attenuated by the inhibition of c-Jun N-terminal kinase (JNK) MAPK activity, chelation of extracellular calcium and calcium channel blocker nifedipine, suggesting that JNK MAPK activity and elevated intracellular calcium level are required for the TP receptor signaling. In conclusion, airway smooth muscle cell TP receptor signaling occurs via JNK MAPK activity and the elevation of extracellular calcium influx, which may provide knowledge for understanding the signaling pathway responsible for the modulation of TP receptor mediated airway hyperresponsiveness to thromboxane.

OriginalsprogEngelsk
TidsskriftEuropean journal of pharmacology
Vol/bind650
Udgave nummer2-3
Sider (fra-til)629-38
Antal sider10
ISSN0031-6970
DOI
StatusUdgivet - 15 jan. 2011
Udgivet eksterntJa

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