Relaxing effects of 5-oxo-ETE on human bronchi involve BK Ca channel activation.
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.
Morin
Caroline
C
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.
Sirois
Marco
M
Echave
Vincent
V
Gomes
Marcio M
MM
Rousseau
Eric
E
D001095:Arachidonic Acids / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects* / Q000502:physiology; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D016210:Methacholine Chloride / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D010455:Peptides / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors / Q000502:physiology*
D001095:Arachidonic Acids; D016085:Bronchoconstrictor Agents; D010455:Peptides; D024681:Potassium Channels, Calcium-Activated; D016210:Methacholine Chloride; C080828:5-oxo-6,8,11,14-eicosatetraenoic acid; C064719:iberiotoxin