title: Potassium ion channels and allergic asthma.
abstract: High-conductive calcium-sensitive potassium channels (BK+Ca) and ATP-sensitive potassium (K+ATP) channels play a significant role in the airway smooth muscle cell and goblet cell function, and cytokine production. The present study evaluated the therapeutic potential of BK+Ca and K+ATP openers, NS 1619 and pinacidil, respectively, in an experimental model of allergic inflammation. Airway allergic inflammation was induced with ovalbumine in guinea pigs during 21 days, which was followed by a 14-day treatment with BK+Ca and K+ATP openers. The outcome measures were airway smooth muscle cells reactivity in vivo and in vitro, cilia beating frequency and the level of exhaled NO (ENO), and the level of pro-inflammatory cytokines in the plasma and bronchoalveolar lavage fluid. The openers of both channels decreased airway smooth muscle cells reactivity, cilia beating frequency, and cytokine levels in the serum. Furthermore, NS1619 reduced ENO and inflammatory cells infiltration. The findings confirmed the presence of beneficial effects of BK+Ca and K+ATP openers on airway defence mechanisms. Although both openers dampened pro-inflammatory cytokines and mast cells infiltration, an evident anti-inflammatory effect was provided only by NS1619. Therefore, we conclude that particularly BK+Ca channels represent a promising new drug target in treatment of airway's allergic inflammation.
authors.affiliation: Department of Pharmacology, Jessenius Faculty of Medicine, Comenius University, Ústav farmakolgie, 26 Sklabinsk St., 036 01, Martin, Slovakia, kocmalova@jfmed.uniba.sk.
authors.forename: M
authors.initials: M
authors.lastname: Kocmalova
authors.forename: M
authors.initials: M
authors.lastname: Oravec
authors.forename: M
authors.initials: M
authors.lastname: Adamkov
authors.forename: V
authors.initials: V
authors.lastname: Sadlonova
authors.forename: I
authors.initials: I
authors.lastname: Kazimierova
authors.forename: I
authors.initials: I
authors.lastname: Medvedova
authors.forename: M
authors.initials: M
authors.lastname: Joskova
authors.forename: S
authors.initials: S
authors.lastname: Franova
authors.forename: M
authors.initials: M
authors.lastname: Sutovska
mesh_terms: D000280:Administration, Inhalation; D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002923:Cilia / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D045853:Exhalation; D006168:Guinea Pigs; D054086:KATP Channels / Q000819:agonists* / Q000378:metabolism; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000819:agonists* / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D049990:Membrane Transport Modulators / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000187:drug effects; D009569:Nitric Oxide / Q000096:biosynthesis; D010047:Ovalbumin; D020110:Pinacidil / Q000494:pharmacology; D010993:Plethysmography, Whole Body; D046509:Tissue Culture Techniques
chemical_list: D001562:Benzimidazoles; D016207:Cytokines; D054086:KATP Channels; D051036:Large-Conductance Calcium-Activated Potassium Channels; D049990:Membrane Transport Modulators; C086491:NS 1619; D009569:Nitric Oxide; D020110:Pinacidil; D010047:Ovalbumin