title: The effect of selective antagonist of H4 receptor JNJ7777120 on nasal symptoms, cough, airway reactivity and inflammation in guinea pigs.
abstract: The efficacy of H4R antagonist JNJ7777120 on nasal symptoms, cough, airway resistance (Raw), inflammatory cell count in bronchoalveolar lavage (BAL) and blood in ovalbumin (OVA) induced allergic rhinitis (AR) was studied in guinea pigs. Animals (n=8) were sensitized by i.p. OVA and were repeatedly challenged with nasal OVA to induce rhinitis, seven animals were not sensitized. Animals were pre-treated with JNJ7777120 2.5 and 5mg/kg i.p. 30 min prior OVA. Cough was induced by inhalation of citric acid, Raw was measured in vivo by Pennock's method as baseline, during AR and after JNJ7777120 treatment. Leucocyte count in BAL and blood was analyzed. JNJ7777120 (5mg/kg) significantly suppressed nasal symptoms and the number of coughs. This compound significantly inhibited airway reactivity to histamine, but not methacholine. Pre-treatment with JNJ7777120 5mg/kg did not influence significantly the leucocyte count in BAL and blood except for a significant decrease in monocyte count in blood compared to the control group (p<0.05). We conclude that the antitussive action of JNJ7777120 is peripheral. The primary effect of the compound is anti-inflammatory, and the suppression of cough is a consequence of reduced airway inflammation.
authors.affiliation: Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Department of Pathological Physiology, Sklabinska Str. 26, 03601 Martin, Slovak Republic.
authors.forename: E
authors.initials: E
authors.lastname: Kovacova-Hanuskova
authors.affiliation: Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Department of Pathological Physiology, Sklabinska Str. 26, 03601 Martin, Slovak Republic.
authors.forename: S
authors.initials: S
authors.lastname: Gavliakova
authors.affiliation: Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Department of Pathological Physiology, Sklabinska Str. 26, 03601 Martin, Slovak Republic.
authors.forename: T
authors.initials: T
authors.lastname: Buday
authors.affiliation: Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Department of Physiology, Mala Hora 4, 03601 Martin, Slovak Republic.
authors.forename: P
authors.initials: P
authors.lastname: Kosutova
authors.affiliation: Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Department of Physiology, Mala Hora 4, 03601 Martin, Slovak Republic.
authors.forename: D
authors.initials: D
authors.lastname: Mokra
authors.affiliation: Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Department of Pharmacology, Sklabinska Str. 26, 03601 Martin, Slovak Republic.
authors.forename: A
authors.initials: A
authors.lastname: Urbanova-Fulmekova
authors.affiliation: Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Department of Pharmacology, Sklabinska Str. 26, 03601 Martin, Slovak Republic.
authors.forename: J
authors.initials: J
authors.lastname: Mokry
authors.affiliation: Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Department of Pathological Physiology, Sklabinska Str. 26, 03601 Martin, Slovak Republic. Electronic address: plevkova@jfmed.uniba.sk.
authors.forename: J
authors.initials: J
authors.lastname: Plevkova
mesh_terms: D000403:Airway Resistance / Q000187:drug effects*; D000536:Aluminum Hydroxide / Q000633:toxicity; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D019343:Citric Acid / Q000633:toxicity; D003371:Cough / Q000139:chemically induced / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007211:Indoles / Q000627:therapeutic use*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D007274:Injections, Intraperitoneal; D009668:Nose Diseases / Q000139:chemically induced / Q000188:drug therapy*; D010047:Ovalbumin / Q000633:toxicity; D010879:Piperazines / Q000627:therapeutic use*; D010991:Plethysmography; D012702:Serotonin Antagonists / Q000627:therapeutic use*
chemical_list: D007211:Indoles; D010879:Piperazines; D012702:Serotonin Antagonists; D019343:Citric Acid; C484309:1-((5-chloro-1H-indol-2-yl)carbonyl)-4-methylpiperazine; D000536:Aluminum Hydroxide; D010047:Ovalbumin
keywords: Airway inflammation; Cough; H4 receptor; Histamine; JNJ7777120