title: Reduction of matrix metalloproteinase-9 activity by the selective phosphodiesterase 4 inhibitor, RP 73-401 in sensitized mice.
abstract: Matrix metalloproteinases are particularly potent in degrading basement membrane collagen and other extracellular matrix components. We have investigated the effects of a selective phosphodiesterase 4 inhibitor, RP 73-401 [N-(3, 5-dichloropyrid-4-yl)-3-cyclopentyloxy-4-methoxybenzamide], on gelatinase (matrix metalloproteinase-2 and matrix metalloproteinase-9) activity in ovalbumin-sensitized and -challenged mice. Twenty-four hours after the last challenge, matrix metalloproteinase activity was evaluated in the bronchoalveolar lavage fluids by a zymography technique, and a significant increase in matrix metalloproteinase-9, but not matrix metalloproteinase-2, activity was noted. When administered orally (0.3-3 mg/kg) 1 h before each ovalbumin challenge, the selective phosphodiesterase 4 inhibitor, RP 73-401, significantly reduced this increased matrix metalloproteinase-9 activity in bronchoalveolar lavage fluids. Our data suggest that RP 73-401 may modulate tissue remodelling associated with lung inflammatory processes including asthma.
authors.affiliation: INSERM U 456, Faculté des Sciences Pharmaceutiques et Biologiques, Université de Rennes 1, 2, Avenue du Prof. Léon Bernard, 35043 cedex, Rennes, France.
authors.forename: C
authors.initials: C
authors.lastname: Belleguic
authors.forename: M
authors.initials: M
authors.lastname: Corbel
authors.forename: N
authors.initials: N
authors.lastname: Germain
authors.forename: E
authors.initials: E
authors.lastname: Boichot
authors.forename: P
authors.initials: P
authors.lastname: Delaval
authors.forename: V
authors.initials: V
authors.lastname: Lagente
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*
chemical_list: D001549:Benzamides; D010726:Phosphodiesterase Inhibitors; D011725:Pyridines; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C087566:piclamilast