{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T03:00:48Z","timestamp":1761102048680},"reference-count":39,"publisher":"American Physiological Society","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2013,4,15]]},"abstract":"<jats:p>Epoxyeicosanoids (EETs) are produced by cytochrome P-450 epoxygenase; however, it is not yet known what triggers their endogenous production in epithelial cells. The relaxing effects of bradykinin are known to be related to endogenous production of epithelial-derived hyperpolarizing factors (EpDHF). Because of their effects on membrane potential, EETs have been reported to be EpDHF candidates (Benoit C, Renaudon B, Salvail D, Rousseau E. Am J Physiol Lung Cell Mol Physiol 280: L965\u2013L973, 2001.). Thus, we hypothesized that bradykinin (BK) may stimulate endogenous EET production in human bronchi. To test this hypothesis, the relaxing and hyperpolarizing effects of BK and 14,15-EET were quantified on human bronchi, as well as the effects of various enzymatic inhibitors on these actions. One micromolar BK or 1 \u03bcM 14,15-EET induced a 45% relaxation on the tension induced by 30 nM U-46619 [a thromboxane-prostanoid (TP)-receptor agonist]. These BK-relaxing effects were reduced by 42% upon addition of 10 nM iberiotoxin [a large-conductance Ca<jats:sup>2+<\/jats:sup>-sensitive K<jats:sup>+<\/jats:sup>(BK<jats:sub>Ca<\/jats:sub>) channel blocker], by 27% following addition of 3 \u03bcM 14,15-epoxyeicosa-5(Z)-enoic acid (an EET antagonist), and by 32% with 3 \u03bcM N-methanesulfonyl-6-(2-propargyloxyphenyl)hexanamide (MS-PPOH, an epoxygenase inhibitor). Hence, BK and 14,15-EET display net hyperpolarizing effects on airway smooth muscle cells that are related to the activation of BK<jats:sub>Ca<\/jats:sub>channels and ultimately yielding to relaxation. Data also indicate that 3 \u03bcM MS-PPOH reduced the hyperpolarizing effects of BK by 43%. Together, the present data support the current hypothesis suggesting a direct relationship between BK and the production of EET regioisomers. Because of its potent anti-inflammatory and relaxing properties, epoxyeicosanoid signaling may represent a promising target in asthma and chronic obstructive pulmonary disease.<\/jats:p>","DOI":"10.1152\/ajplung.00379.2012","type":"journal-article","created":{"date-parts":[[2013,2,16]],"date-time":"2013-02-16T02:35:16Z","timestamp":1360982116000},"page":"L562-L569","source":"Crossref","is-referenced-by-count":7,"title":["Relationship between bradykinin-induced relaxation and endogenous epoxyeicosanoid synthesis in human bronchi"],"prefix":"10.1152","volume":"304","author":[{"given":"Yacine","family":"Tabet","sequence":"first","affiliation":[{"name":"Le Bilarium, Department of Physiology and Biophysics, Universit\u00e9 de Sherbrooke, Sherbrooke, Quebec, Canada;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Sirois","sequence":"additional","affiliation":[{"name":"Service of Thoracic Surgery, Universit\u00e9 de Sherbrooke, Sherbrooke, Quebec, Canada; 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