PMID- 21821730 OWN - NLM STAT- MEDLINE DCOM- 20111222 LR - 20200930 IS - 1522-1504 (Electronic) IS - 1040-0605 (Linking) VI - 301 IP - 5 DP - 2011 Nov TI - Improved bioavailability of epoxyeicosatrienoic acids reduces TP-receptor agonist-induced tension in human bronchi. PG - L675-82 LID - 10.1152/ajplung.00427.2010 [doi] AB - Epoxyeicosatrienoic acid (EET) and thromboxane A(2) are arachidonic acid derivatives. The former has initially been defined as an epithelium-derived hyperpolarizing factor displaying broncho-relaxing and anti-inflammatory properties, as recently demonstrated, whereas thromboxane A(2) induces vaso- and bronchoconstriction upon binding to thromboxane-prostanoid (TP)-receptor. EETs, however, are quickly degraded by the soluble epoxide hydrolase (sEH) into inactive diol compounds. The aim of this study was to investigate the effects of 14,15-EET on TP-receptor activation in human bronchi. Tension measurements performed on native bronchi from various species, acutely treated with increasing 14,15-EET concentrations, revealed specific and concentration-dependent relationships as well as a decrease in the tension induced by 30 nM U-46619, used as a synthetic TP-receptor agonist. Interestingly, acute treatments with 3 muM N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide, an epoxygenase inhibitor, which minimizes endogenous production of EET, resulted in an increased reactivity to U-46619. Furthermore, we demonstrated that chronic treatments with trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB), a sEH inhibitor, reduced human bronchi reactivity to U-46619. During our tension measurements, we also observed that human bronchi generated small-amplitude contractions; these spontaneous activities were reduced upon acute 14,15-EET treatments in the presence of t-AUCB. Altogether, these data demonstrate that endogenous and exogenous 14,15-EET could interfere with the activation of TP-receptors as well as with spontaneous oscillations in human airway smooth muscle tissues. FAU - Senouvo, Farid Yannick AU - Senouvo FY AD - Le Bilarium, Department of Physiology and Biophysics, Faculty of Medicine and Health Sciences, Universite de Sherbrooke, Sherbrooke, Quebec, Canada. FAU - Tabet, Yacine AU - Tabet Y FAU - Morin, Caroline AU - Morin C FAU - Albadine, Roula AU - Albadine R FAU - Sirois, Chantal AU - Sirois C FAU - Rousseau, Eric AU - Rousseau E LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110805 PL - United States TA - Am J Physiol Lung Cell Mol Physiol JT - American journal of physiology. Lung cellular and molecular physiology JID - 100901229 RN - 0 (4-(4-(3-adamantan-1-ylureido)cyclohexyloxy)benzoic acid) RN - 0 (Benzoates) RN - 0 (Epoxy Compounds) RN - 0 (Receptors, Prostaglandin E) RN - 0 (Receptors, Thromboxane) RN - 27YG812J1I (Arachidonic Acid) RN - 57576-52-0 (Thromboxane A2) RN - 76898-47-0 (15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid) RN - 81276-03-1 (14,15-epoxy-5,8,11-eicosatrienoic acid) RN - 8W8T17847W (Urea) RN - AAN7QOV9EA (Eicosapentaenoic Acid) RN - EC 3.3.2.- (Epoxide Hydrolases) RN - FC398RK06S (8,11,14-Eicosatrienoic Acid) SB - IM MH - 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid/pharmacology MH - 8,11,14-Eicosatrienoic Acid/*analogs & derivatives/pharmacology MH - Animals MH - Arachidonic Acid/metabolism MH - Benzoates/pharmacology MH - Blotting, Western MH - Bronchi/cytology/*drug effects/physiology MH - Cells, Cultured MH - Eicosapentaenoic Acid/metabolism MH - Electrophoresis, Polyacrylamide Gel MH - Epoxide Hydrolases/antagonists & inhibitors/metabolism MH - Epoxy Compounds MH - Fluorescent Antibody Technique MH - Guinea Pigs MH - Humans MH - Mice MH - Muscle Tonus/*drug effects MH - Muscle, Smooth/cytology/*drug effects/physiology MH - Myocytes, Smooth Muscle/cytology/*drug effects/physiology MH - Rats MH - Receptors, Prostaglandin E/agonists/antagonists & inhibitors/*metabolism MH - Receptors, Thromboxane/agonists/antagonists & inhibitors/*metabolism MH - *Signal Transduction MH - Thromboxane A2/metabolism MH - Urea/analogs & derivatives/pharmacology EDAT- 2011/08/09 06:00 MHDA- 2011/12/23 06:00 CRDT- 2011/08/09 06:00 PHST- 2011/08/09 06:00 [entrez] PHST- 2011/08/09 06:00 [pubmed] PHST- 2011/12/23 06:00 [medline] AID - ajplung.00427.2010 [pii] AID - 10.1152/ajplung.00427.2010 [doi] PST - ppublish SO - Am J Physiol Lung Cell Mol Physiol. 2011 Nov;301(5):L675-82. doi: 10.1152/ajplung.00427.2010. Epub 2011 Aug 5.