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: C Belleguic, M Corbel, N Germain, E Boichot, P Delaval, V Lagente
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 404 Issue 3 Pg. 369-73 (Sep 22 2000) ISSN: 0014-2999 [Print] Netherlands
• PMID: 10996602 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzamides
• Phosphodiesterase Inhibitors
• Pyridines
• 3',5'-Cyclic-AMP Phosphodiesterases
• Cyclic Nucleotide Phosphodiesterases, Type 4
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9
• piclamilast

Topics

• 3',5'-Cyclic-AMP Phosphodiesterases (antagonists & inhibitors, metabolism)
• Animals
• Benzamides (pharmacology)
• Bronchoalveolar Lavage Fluid
• Cyclic Nucleotide Phosphodiesterases, Type 4
• Male
• Matrix Metalloproteinase 2 (drug effects, metabolism)
• Matrix Metalloproteinase 9 (drug effects, metabolism)
• Mice
• Mice, Inbred BALB C
• Phosphodiesterase Inhibitors (pharmacology)
• Pyridines (pharmacology)