Correlations of PDE-4 inhibition between enzymes of smooth muscle and inflammatory cell sources.
The sensitivities of PDE-4 enzymes from smooth muscle and inflammatory cell sources from different species to a range of structurally diverse compounds were compared. All inflammatory cell PDE-4 sources displayed good crosscorrelations in their sensitivity to inhibition by these compounds. Similarly, PDE-4 enzymes from smooth muscle sources were well-correlated; however, there was no crosscorrelation between PDE-4 from smooth muscle sources and those of inflammatory cell sources, possibly reflecting differences in subcellular location of enzymes as well as subtype expression. The present study concludes that PDE-4 preparations from smooth muscle sources as well as those from inflammatory cell sources may be used to model the potential smooth muscle cell relaxing properties and anti-inflammatory properties of a compound in relation to human asthma.
Cariuk
P
P
Napp Research Centre, Cambridge Science Park, Cambridge, UK.
Cavalla
D
D
Chasin
M
M
Giembycz
M
M
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D002417:Cattle; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D006168:Guinea Pigs; D006801:Humans; D007962:Leukocytes / Q000201:enzymology*; D008168:Lung / Q000201:enzymology; D008297:Male; D009130:Muscle, Smooth / Q000201:enzymology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D014132:Trachea / Q000201:enzymology
D010726:Phosphodiesterase Inhibitors; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4