Reduced airway hyperresponsiveness by phosphodiesterase 3 and 4 inhibitors in guinea-pigs.
The aim of the present study was to compare the effects of selective phosphodiesterase (PDE) 3, 4 and 5 inhibitors on antigen-induced airway hyperresponsiveness in sensitized guinea-pigs. When the sensitized guinea-pigs were orally pre-treated with the selective PDE4 inhibitor, Ro 20-1724 (30 mg/kg), and studied 48h after OA, a significant reduction (P<0.01) of the leftward shift of the dose-response curve to ACh was noted, whereas it was ineffective at the lower dose (10 mg/kg). Administration of the selective PDE3 inhibitor, milrinone (30 mg/kg) also elicited a significant reduction (P<0.01) of the airway hyperresponsiveness, whereas the PDE5 inhibitor zaprinast (30 mg/kg) was ineffective. These results show that both PDE3 and PDE4 inhibitors are able to inhibit the antigen-induced airway hyperresponsiveness in sensitized guinea-pigs and support the potential utility of selective PDE inhibitors in the treatment of asthma.
Germain
N
N
INSERM U456, Laboratoire de Pharmacodynamie et de Pharmacologie Moléculaire, Faculté des Sciences Pharmaceutiques et Biologiques, Université de Rennes 1, France.
Boichot
E
E
Planquois
J M
JM
Lagente
V
V
D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000627:therapeutic use*; D000109:Acetylcholine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D006168:Guinea Pigs; D008297:Male; D020105:Milrinone / Q000627:therapeutic use*; D010047:Ovalbumin; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D011688:Purinones / Q000627:therapeutic use; D012130:Respiratory Hypersensitivity / Q000188:drug therapy* / Q000503:physiopathology*
D010726:Phosphodiesterase Inhibitors; D011688:Purinones; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D010047:Ovalbumin; C011145:zaprinast; D020105:Milrinone; D000109:Acetylcholine