Transport Physiology

Pflügers Archiv - European Journal of Physiology

, Volume 463, Issue 3, pp 497-509

First online:

Allergic sensitization enhances anion current responsiveness of murine trachea to PAR-2 activation

  • Juraj RievajAffiliated withPulmonary Research Group, Department of Medicine, University of AlbertaDepartment of Physiology, University of Alberta
  • , Courtney DavidsonAffiliated withPulmonary Research Group, Department of Medicine, University of Alberta
  • , Ahmed NadeemAffiliated withPulmonary Research Group, Department of Medicine, University of Alberta
  • , Morley HollenbergAffiliated withDepartment of Pharmacology and Therapeutics, University of Calgary
  • , Marek DuszykAffiliated withDepartment of Physiology, University of Alberta
  • , Harissios VliagoftisAffiliated withPulmonary Research Group, Department of Medicine, University of Alberta Email author 

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Abstract

Protease-activated receptor 2 (PAR-2) is a G protein-coupled receptor possibly involved in the pathogenesis of asthma. PAR-2 also modulates ion transport in cultured epithelial cells, but these effects in native airways are controversial. The influence of allergic inflammation on PAR-2-induced changes in ion transport has received little attention. Here, we studied immediate changes in transepithelial short circuit current (I sc) induced by PAR-2 activation in the tracheas of naive and allergic mice. Activation of PAR-2 with an apically added activation peptide (AP) induced a small increase in I sc, while a much larger increase was observed following basolateral AP addition. In ovalbumin-sensitized and -challenged animals used as a model of allergic airway inflammation, the effect of basolateral AP addition was enhanced. Responses to basolateral AP in both naive and allergic mice were not decreased by blocking sodium absorption with amiloride or CFTR function with CFTRinh172 but were reduced by the cyclooxygenase inhibitor indomethacin and largely blocked (>80%) by niflumic acid, a calcium-activated chloride channels’ (CaCC) blocker. Allergic mice also showed an enhanced response to ATP and thapsigargin. There was no change in mRNA expression of Par-2 or of the chloride channels Ano1 (Tmem16a) and Bestrophin 2 in tracheas from allergic mice, while mRNA levels of Bestrophin 1 were increased. In conclusion, basolateral PAR-2 activation in the mouse airways led to increased anion secretion through apical CaCC, which was more pronounced in allergic animals. This could be a protective mechanism aimed at clearing allergens and defending against mucus plugging.

Keywords

PAR-2 Asthma Bestrophin Airway surface liquid Calcium-activated chloride channels