The effect of long-term administered CRAC channels blocker on the functions of respiratory epithelium in guinea pig allergic asthma model.
Previously, therapeutic potency of CRAC channels blocker was evidenced as a significant decrease in airway smooth muscle hyperreactivity, antitussive and anti-inflammatory effects. The major role of the respiratory epithelium in asthma pathogenesis was highlighted only recently and CRAC channels were proposed as the most significant route of Ca2+ entry into epithelial cells. The aim of the study was to analyse the impact of long-term administered CRAC channels blocker on airway epithelium, e.g. cytokine production and ciliary beat frequency (CBF) using an animal model of allergic asthma. Ovalbumin-induced allergic airway inflammation of guinea pigs was followed by long-term (14 days lasted) therapy by CRAC blocker (3-fluoropyridine-4-carboxylic acid, FPCA). The influence of long-term therapy on cytokines (IL-4, IL-5 and IL-13) in BALF and in plasma, immunohistochemical staining of pulmonary tissue (c-Fos positivity) and CBF in vitro were used for analysis. Decrease in cytokine levels and in c-Fos positivity confirmed an anti-inflammatory effect of long-term administered FPCA. Cytokine levels in BALF and distribution of c-Fos positivity suggested that FPCA was a more potent inhibitor of respiratory epithelium secretory functions than budesonide. FPCA and budesonide reduced CBF only insignificantly. All findings supported CRAC channels as promising target in the new strategy of antiasthmatic treatment.
Department of Pharmacology, Jessenius Faculty of Medicine, Comenius University, Sklabinska Street 26, 036 01 Martin, Slovak Republic. sutovska@jfmed.uniba.sk.
Martina
M
Sutovska
Michaela
M
Kocmalova
Marta
M
Joskova
Marian
M
Adamkov
Sona
S
Franova
D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology*; D002121:Calcium Channel Blockers / Q000008:administration & dosage; D015220:Calcium Channels / Q000276:immunology*; D020013:Calcium Signaling / Q000187:drug effects / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D006168:Guinea Pigs; D007539:Isonicotinic Acids / Q000008:administration & dosage*; D008137:Longitudinal Studies; D008297:Male; D010047:Ovalbumin; D020545:Respiratory Mucosa / Q000187:drug effects / Q000276:immunology*; D016896:Treatment Outcome
C576491:3-fluoropyridine-4-carboxylic acid; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D016207:Cytokines; D007539:Isonicotinic Acids; D010047:Ovalbumin