Effects of isoenzyme selective phosphodiesterase inhibitors on bacterial lipopolysaccharide-induced bronchial hyperreactivity in guinea pigs.
1. Effects of cilostazol and vesnarinone (selective PDE III inhibitors), rolipram (selective PDE IV inhibitor) and theophylline (nonselective PDE inhibitor) on LPS-induced bronchial hyperreactivity were investigated in guinea pigs. 2. Cilostazol (50 mg/kg PO), vesnarinone (100 mg/kg PO), rolipram (20 mg/kg PO), and theophylline (50 mg/kg PO), significantly inhibited bronchial hyperreactivity to acetylcholine (Ach) and TNF release into bronchoalveolar lavage fluid following LPS exposure. None of these compounds influenced neutrophil influx into bronchoalveolar lavage fluid. 3. Rolipram and theophylline antagonized Ach-induced bronchoconstriction in normal guinea pigs.
Uno
T
T
Department of Pharmacology, Gifu Pharmaceutical University, Mitahorahigashi, Japan.
Tanaka
H
H
Nagai
H
H
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000201:enzymology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D000077407:Cilostazol; D006168:Guinea Pigs; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009504:Neutrophils; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011719:Pyrazines; D011760:Pyrrolidinones / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D020889:Rolipram; D013777:Tetrazoles / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007527:Isoenzymes; D008070:Lipopolysaccharides; D010726:Phosphodiesterase Inhibitors; D011719:Pyrazines; D011760:Pyrrolidinones; D011804:Quinolines; D013777:Tetrazoles; D014409:Tumor Necrosis Factor-alpha; C041667:vesnarinone; D013806:Theophylline; D020889:Rolipram; D000077407:Cilostazol; D000109:Acetylcholine