title: Effects of Selective Inhibition of PDE4 by YM976 on Airway Reactivity and Cough in Ovalbumin-Sensitized Guinea Pigs.
abstract: Phosphodiesterases (PDEs) are enzymes involved in the degradation of cAMP and cGMP. Selective PDE4 inhibitors (e.g., roflumilast) are effective in therapy of chronic obstructive pulmonary disease associated with neutrophil inflammation. The aim of this study was to evaluate the effects of a selective PDE4 inhibitor, YM976, on citric acid-induced cough, in vivo and in vitro airway smooth muscle reactivity to histamine, and on inflammatory mediators in ovalbumin-sensitized guinea pigs, with experimentally induced eosinophil inflammation. The YM976 was administered intraperitoneally at a dose of 1.0 mg/kg once daily for 7 days. Sensitization with ovalbumin led to a significant increase in the number of coughs, and in vivo and in vitro airway reactivity. Also, increased plasma levels of IL-4, IL-5, and PAF were observed, with a significant increase in the differential count of eosinophils in both blood and bronchoalveolar lavage fluid. The YM976 suppressed the number of coughs, the airway reactivity in tracheal tissue strips, and the IL-4 level. The findings indicate that PDE4 inhibition by YM976 exerts antitussive and anti-inflammatory effects in guinea pigs with ovalbumin-induced eosinophilic inflammation.
authors.affiliation: Biomedical Center (BioMed) Martin, Division of Respirology and Department of Pharmacology, Jessenius School of Medicine in Martin, Comenius University in Bratislava, Mala Hora 4C, SK-03601, Martin, Slovakia. mokry@jfmed.uniba.sk.
authors.forename: J
authors.initials: J
authors.lastname: Mokrý
authors.affiliation: Biomedical Center (BioMed) Martin, Division of Respirology and Department of Pharmacology, Jessenius School of Medicine in Martin, Comenius University in Bratislava, Mala Hora 4C, SK-03601, Martin, Slovakia.
authors.forename: A
authors.initials: A
authors.lastname: Urbanová
authors.affiliation: Biomedical Center (BioMed) Martin, Division of Respirology and Department of Pharmacology, Jessenius School of Medicine in Martin, Comenius University in Bratislava, Mala Hora 4C, SK-03601, Martin, Slovakia.
authors.forename: I
authors.initials: I
authors.lastname: Medvedová
authors.affiliation: Biomedical Center (BioMed) Martin, Division of Respirology and Department of Pharmacology, Jessenius School of Medicine in Martin, Comenius University in Bratislava, Mala Hora 4C, SK-03601, Martin, Slovakia.
authors.forename: M
authors.initials: M
authors.lastname: Kertys
authors.affiliation: Biomedical Center (BioMed) Martin, Division of Respirology and Department of Physiology, Jessenius School of Medicine in Martin, Comenius University in Bratislava, Mala Hora 4C, SK-03601, Martin, Slovakia.
authors.forename: P
authors.initials: P
authors.lastname: Mikolka
authors.affiliation: Biomedical Center (BioMed) Martin, Division of Respirology and Department of Physiology, Jessenius School of Medicine in Martin, Comenius University in Bratislava, Mala Hora 4C, SK-03601, Martin, Slovakia.
authors.forename: P
authors.initials: P
authors.lastname: Kosutová
authors.affiliation: Biomedical Center (BioMed) Martin, Division of Respirology and Department of Physiology, Jessenius School of Medicine in Martin, Comenius University in Bratislava, Mala Hora 4C, SK-03601, Martin, Slovakia.
authors.forename: D
authors.initials: D
authors.lastname: Mokrá
mesh_terms: D000818:Animals; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D003371:Cough / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000737:chemistry*; D006168:Guinea Pigs; D008297:Male; D010047:Ovalbumin / Q000633:toxicity*; D058988:Phosphodiesterase 4 Inhibitors / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D011744:Pyrimidinones / Q000494:pharmacology*; D012137:Respiratory System / Q000187:drug effects*
chemical_list: D058988:Phosphodiesterase 4 Inhibitors; D011725:Pyridines; D011744:Pyrimidinones; C414544:YM 976; D010047:Ovalbumin; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4
keywords: Airway reactivity; Animal model; Citric acid; Histamine; Inflammation; Interleukins; Organ bath; Phosphodiesterase inhibitors