ABCD of the phosphodiesterase family: interaction and differential activity in COPD.
Phosphodiesterases (PDEs) are important enzymes that hydrolyze the cyclic nucleotides adenosine 3'5'-cyclic monophosphate (cAMP) and guanosine 3'5'-cyclic monophosphate (cGMP) to their inactive 5' monophosphates. They are highly conserved across species and as well as their role in signal termination, they also have a vital role in intra-cellular localization of cyclic nucleotide signaling and integration of the cyclic nucleotide pathways with other signaling pathways. Because of their pivotal role in intracellular signaling, they are now of considerable interest as therapeutic targets in a wide variety diseases, including COPD where PDE inhibitors may have bronchodilator, anti-inflammatory and pulmonary vasodilator actions. This review examines the diversity and cellular localization of the isoforms of PDE, the known and speculative relevance of this to the treatment of COPD, and the range of PDE inhibitors in development together with a discussion of their possible role in treating COPD.
Halpin
David M G
DM
Royal Devon and Exeter Hospital, Exeter EX2 5DW, UK. david.halpin@rdeft.nhs.uk
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes; D008168:Lung / Q000187:drug effects / Q000201:enzymology*; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000201:enzymology*; D019141:Respiratory System Agents / Q000627:therapeutic use; D015290:Second Messenger Systems / Q000187:drug effects
D007527:Isoenzymes; D010726:Phosphodiesterase Inhibitors; D019141:Respiratory System Agents; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases