title: CRAC ion channels and airway defense reflexes in experimental allergic inflammation.
abstract: Calcium release-activated calcium channels (CRAC) play unambiguous role in secretory functions of mast cells, T cells, and eosinophils. Less knowledge exists about the role of CRAC, widely distributed in airway smooth muscle (ASM) cells, in airway contractility. The presented study seeks to determine the possible participation of CRAC in ASM-based inflammatory airway disorders in guinea pigs. The acute and long-term administration (14 days) of the CRAC antagonist 3-fluoropyridine-4-carboxylic acid was used to examine the ASM contractility and associated reflexes in the guinea pig model of allergic airway inflammation by the following methods: (i) evaluation of specific airway resistance in vivo; (ii) evaluation of the contractile response of isolated ASM strips in vitro; and (iii) citric acid-induced cough reflex; (iv) measurement of exhaled NO levels (E(NO)). Allergic airway inflammation was induced by repetitive exposure of guinea pigs to ovalbumin (10(-6) M). The CRAC antagonist administered in a single dose to guinea pigs with confirmed allergic inflammation significantly reduced the cough response and the airway resistance, which corresponded with the findings in vitro. Long-term application of the CRAC antagonist had more strongly expressed effects. The results confirm the role of CRAC in the pathophysiology of experimental animal asthma and have a potential meaning for anti-asthma therapy.
authors: Department of Pharmacology, Comenius University, Martin, Slovakia. sutovska@jfmed.uniba.sk
authors: M
authors: M
authors: Sutovska
authors: M
authors: M
authors: Adamkov
authors: M
authors: M
authors: Kocmalova
authors: L
authors: L
authors: Mesarosova
authors: M
authors: M
authors: Oravec
authors: S
authors: S
authors: Franova
mesh_terms: D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology; D001249:Asthma / Q000188:drug therapy*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000378:metabolism*; D003371:Cough; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004804:Eosinophils / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy*; D007539:Isonicotinic Acids / Q000494:pharmacology*; D008297:Male; D008407:Mast Cells / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000032:analysis; D010047:Ovalbumin / Q000008:administration & dosage; D012137:Respiratory System / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: C576491:3-fluoropyridine-4-carboxylic acid; D018927:Anti-Asthmatic Agents; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007539:Isonicotinic Acids; D009569:Nitric Oxide; D010047:Ovalbumin; D002118:Calcium