title: TRPV4 antagonist GSK2193874 does not modulate cough response to osmotic stimuli.
abstract: Osmolarity changes of airway superficial fluid are associated with cough and are used in research. TRPV4 is calcium channel initially described as osmosensor. In the airways, it can play role in increasing cough reflex sensitivity. The aim of our study was to test whether cough to osmotic stimuli is mediated via TRPV4 channel. Cough response was measured in 12 male guinea pigs by inhalation of saline, distilled water, hypertonic solution and citric acid for 10min in whole-body plethysmograph. Data were obtained in naïve animals and after pre-treatment with selective TRPV4 antagonist GSK2193874 in doses 300μg/kg (GSK300) and 900μg/kg (GSK900). Cough response to all tested aerosols was significantly higher than to saline. Pre-treatment with GSK300 did not influence response to osmotic stimuli - only reduced cough to citric acid. GSK900 reduced cough response to hypotonic stimuli and citric acid. TRPV4 mediated activation of airway afferents does not seem to be the exclusive mechanism responsible for cough to osmotic stimuli.
authors.affiliation: Jessenius Faculty of Medicine in Martin, Biomedical Center Martin JFM CU, Comenius University in Bratislava, Slovakia; Jessenius Faculty of Medicine in Martin, Department of Pathophysiology JFM CU, Comenius University in Bratislava, Slovakia. Electronic address: buday@jfmed.uniba.sk.
authors.forename: Tomas
authors.initials: T
authors.lastname: Buday
authors.affiliation: Jessenius Faculty of Medicine in Martin, Department of Pathophysiology JFM CU, Comenius University in Bratislava, Slovakia.
authors.forename: Lea
authors.initials: L
authors.lastname: Kovacikova
authors.affiliation: Jessenius Faculty of Medicine in Martin, Department of Pathophysiology JFM CU, Comenius University in Bratislava, Slovakia.
authors.forename: Robert
authors.initials: R
authors.lastname: Ruzinak
authors.affiliation: Jessenius Faculty of Medicine in Martin, Biomedical Center Martin JFM CU, Comenius University in Bratislava, Slovakia; Jessenius Faculty of Medicine in Martin, Department of Pathophysiology JFM CU, Comenius University in Bratislava, Slovakia; Jessenius Faculty of Medicine in Martin, Simulation Education Center JFM CU, Comenius University in Bratislava, Slovakia.
authors.forename: Jana
authors.initials: J
authors.lastname: Plevkova
mesh_terms: D000818:Animals; D019343:Citric Acid / Q000008:administration & dosage; D003371:Cough / Q000209:etiology* / Q000517:prevention & control*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D008297:Male; D009994:Osmolar Concentration; D009997:Osmotic Pressure; D010812:Physical Stimulation / Q000009:adverse effects; D010991:Plethysmography; D018709:Statistics, Nonparametric; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors*; D014851:Wakefulness
chemical_list: D050916:TRPV Cation Channels; C416986:TRPV4 protein, human; D019343:Citric Acid
keywords: Citric acid; Cough; GSK2193874; Osmolarity; TRPV4