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A novel approach to bronchodilation: combining the Kv7 channel activator retigabine with the β2‐adrenergic agonist formoterol (660.9)
Author(s) -
Haick Jennifer,
Brueggemann Lioubov,
Byron Kenneth
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.660.9
Subject(s) - bronchodilation , formoterol , bronchoconstriction , methacholine , bronchodilator , formoterol fumarate , agonist , pharmacology , activator (genetics) , chemistry , histamine , potassium channel , adrenergic , medicine , endocrinology , asthma , lung , receptor , respiratory disease , budesonide
Kv7 potassium channels are expressed in airway smooth muscle cells (ASMCs) and bronchoconstrictor agonists, such as methacholine and histamine, inhibit Kv7 currents. Inhibition of Kv7 channels in rat and human airways is sufficient to induce bronchoconstriction. Long‐acting β2‐adrenergic agonists (LABAs) are commonly used in the treatment of asthma. However, long term use of these drugs may lead to tolerance. Here we provide evidence that the Kv7 channel activator retigabine can oppose agonist‐induced suppression of Kv7 currents and enhance bronchodilation by the LABA formoterol. Dose‐dependent bronchodilation by retigabine and formoterol was measured using rat precision cut lung slices (PCLS). A submaximal dose of formoterol (10nM) induced relaxation of methacholine‐constricted airways, but this relaxation was transient despite continued treatment. The approximate EC50 dose of retigabine (10µM) enhanced formoterol‐induced relaxation and eliminated the apparent desensitization. Similar results were obtained in human PCLS pre‐constricted with histamine, suggesting a beneficial effect of combining a Kv7 channel activator with standard bronchodilator therapy. Grant Funding Source : Supported by Loyola University Chicago