title: The long-term administration of Orai 1 antagonist possesses antitussive, bronchodilatory and anti-inflammatory effects in experimental asthma model.
abstract: The best-studied store-operated Ca2+ channels (SOCs), Ca2+ release activated Ca2+ (CRAC) channels, are activated by depleting endoplasmic reticulum Ca2+ pool and mediate Ca2+ influx vitally important for Ca2+ restoration and many cellular function. CRAC channels were identified on immune and airway smooth muscle (ASM) cells. Emerging evidence points to its involvement in allergic airways diseases. This article evaluated therapeutic potency of CRAC antagonist in experimental animal model of allergic asthma. Allergic asthma, induced by repetitive exposure of guinea pigs to ovalbumine, was followed by 14 days therapy by CRAC antagonist (3-fluoropyridine-4-carboxylic acid, FPCA). In vivo changes of specific airways resistance (sRaw) evaluated bronchodilatory effect of FPCA and salbutamol. The method of citric acid-induced cough reflex assessed antitussive activity of FPCA and codeine. The measurement of exhaled NO (ENO), expression of inducible NO-synthase (iNOS) by RT-PCR and immunohistochemical staining of airways tissue verified anti-inflammatory effect of FPCA. Long-term administration of FPCA resulted in significant cough suppression and bronchodilation, both comparable to the effect of control drugs. FPCA significantly decreased ENO and iNOS expression, which together with immunohistochemical analysis validated its anti-inflammatory effect. Presented data confirmed CRAC channels as a promising target for treatment of respiratory diseases associated with allergic inflammation.
authors.affiliation: Department of Pharmacology, Comenius University, Martin, Slovak Republic. sutovska@jfmed.uniba.sk
authors.forename: Martina
authors.initials: M
authors.lastname: Sutovská
authors.forename: Michaela
authors.initials: M
authors.lastname: Kocmálová
authors.forename: Marian
authors.initials: M
authors.lastname: Adamkov
authors.forename: Desanka
authors.initials: D
authors.lastname: Výbohová
authors.forename: Pavol
authors.initials: P
authors.lastname: Mikolka
authors.forename: Daniela
authors.initials: D
authors.lastname: Mokrá
authors.forename: Jozef
authors.initials: J
authors.lastname: Hatok
authors.forename: Martina
authors.initials: M
authors.lastname: Antošová
authors.forename: Soňa
authors.initials: S
authors.lastname: Fraňová
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D000996:Antitussive Agents / Q000008:administration & dosage*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology*; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D006168:Guinea Pigs; D008137:Longitudinal Studies; D008168:Lung / Q000187:drug effects / Q000503:physiopathology*; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D000996:Antitussive Agents; D001993:Bronchodilator Agents; D002121:Calcium Channel Blockers