Author:
Morin Caroline,Sirois Marco,Echave Vincent,Gomes Marcio M.,Rousseau Eric
Abstract
Airway smooth muscle (ASM) metabolizes arachidonic acid (AA) through various enzymatic pathways, including cytochrome P-450 (CYP-450) ω-hydroxylase, which leads to the production of 20-hydroxyeicosatetraenoic acid (20-HETE). The goal of this study was to delineate the mode of action of 20-HETE in human ASM cells. Isometric tension measurements demonstrated that 20-HETE induced a concentration-dependent relaxant effect in ASM on bronchi precontracted with either methacholine or AA. Relaxing effects of 20-HETE on resting tone were prevented by 10 nM iberiotoxin (IbTx), a BKCa channel inhibitor. Microelectrode measurements showed that exogenous additions of 20-HETE (0.1–10 μM) hyperpolarized the membrane potential of human ASM cells. This concentration-dependent electrophysiological effect induced by the eicosanoid was prevented by 10 nM IbTx. Complementary experiments, using the planar lipid bilayer reconstitution technique, demonstrated that 20-HETE activated reconstituted BKCa channels at low free Ca2+ concentrations. Together, these results indicate that 20-HETE-dependent activation of BKCa channels is responsible for the hyperpolarization and controlled relaxation of ASM in human distal bronchi.
Publisher
American Physiological Society
Subject
Cell Biology,Physiology (medical),Pulmonary and Respiratory Medicine,Physiology
Cited by
34 articles.
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