Morin Caroline, Sirois Marco, Echave Vincent, Gomes Marcio M, Rousseau Eric
Le Bilarium, Department of Physiology and Biophysics, Faculty of Medicine and Health Sciences, Université de Sherbrooke 3001, 12th Avenue North, Sherbrooke J1H 5N4, Que., Canada.
Prostaglandins Other Lipid Mediat. 2007 Jun;83(4):311-9. doi: 10.1016/j.prostaglandins.2007.03.001. Epub 2007 Mar 7.
The present study investigated the ability of 5-oxo-EicosaTetraEnoic acid (5-oxo-ETE) for modulating airway smooth muscle (ASM) tone in human bronchi. 5-Oxo-ETE induced a concentration-dependent relaxing effect on human bronchi pre-contracted with methacholine (MCh) and arachidonic acid (AA). This relaxing response was highly sensitive to Iberiotoxin (IbTx), a large conducting Ca(2+)-activated K(+) channel (BK(Ca)) inhibitor. Furthermore, microelectrode measurements revealed that 5-oxo-ETE (0.1-10 microM) hyperpolarizes the membrane potential of human bronchial ASM cells. These hyperpolarizing effects were also inhibited in the presence of 10nM IbTx. Lastly, 5-oxo-ETE was shown to directly activate reconstituted BK(Ca) channels derived from human airway smooth muscles. In summary, the 5-oxo-ETE eicosanoid activates a specific K(+) conductance, involved in membrane hyperpolarization, which in turn reduces Ca(2+) entry and facilitates relaxation of smooth muscle cells.
本研究调查了5-氧代-二十碳四烯酸（5-oxo-ETE）调节人支气管气道平滑肌（ASM）张力的能力。5-氧代-ETE对用乙酰甲胆碱（MCh）和花生四烯酸（AA）预收缩的人支气管产生浓度依赖性舒张作用。这种舒张反应对大电导钙激活钾通道（BK（Ca））抑制剂iberiotoxin（IbTx）高度敏感。此外，微电极测量显示5-氧代-ETE（0.1-10 microM）使人类支气管ASM细胞膜电位超极化。在存在10nM IbTx的情况下，这些超极化作用也受到抑制。最后，5-氧代-ETE被证明可直接激活源自人气道平滑肌的重组BK（Ca）通道。总之，5-氧代-ETE类花生酸激活一种特定的钾电导，参与膜超极化，进而减少钙内流并促进平滑肌细胞舒张。
