Effects of inhaled glaucine on pulmonary responses to antigen in sensitized guinea pigs.
The alkaloid (S)-(+)-1,2,9,10-tetramethoxyaporphine (glaucine) is a phosphodiesterase 4 inhibitor with bronchodilator and anti-inflammatory activity in vitro. In this study, we examined the in vivo effects of glaucine on an animal model of asthma. In ovalbumin sensitized guinea pigs, inhaled glaucine (10 mg ml(-1), 3 min) inhibited the acute bronchoconstriction produced by aerosol antigen (antigen response was 256+/-42 and 95+/-14 cm H(2)O l(-1) s(-1) in control and glaucine-treated animals, respectively; P<0.05). Pretreatment with glaucine (10 mg ml(-1), 10 min inhalation, 30 min pre- and 3 h post-antigen exposure) markedly reduced airway hyperreactivity to histamine, eosinophil lung accumulation, and increased eosinophil peroxidase activity in bronchoalveolar lavage fluid 24 h after exposure of conscious guinea pigs to aerosol antigen. In addition, inhaled glaucine (5-10 mg ml(-1), 3 min) inhibited the microvascular leakage produced after inhaled antigen at all airway levels. These data support the potential interest of phosphodiesterase 4 inhibitors in asthma treatment.
Pons
R
R
Departament de Farmacologia, Facultat de Medicina i Odontologia, Universitat de València, Av. Blasco Ibáñez 15, E-46010, Valencia, Spain.
Santamaría
P
P
Suchankova
J
J
Cortijo
J
J
Morcillo
E J
EJ
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D000941:Antigens / Q000008:administration & dosage*; D001060:Aporphines / Q000494:pharmacology*; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000517:prevention & control; D016084:Bronchoconstriction / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D004305:Dose-Response Relationship, Drug; D047209:Eosinophil Peroxidase; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D008297:Male; D010544:Peroxidases / Q000187:drug effects / Q000378:metabolism; D011652:Pulmonary Circulation / Q000187:drug effects; D014132:Trachea / Q000187:drug effects / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects
D000941:Antigens; D001060:Aporphines; D006632:Histamine; D000242:Cyclic AMP; D047209:Eosinophil Peroxidase; D010544:Peroxidases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C005004:glaucine