Targeting phosphodiesterases in anti-platelet therapy.
There are two primary modes of platelet inhibition: blockade of membrane receptors or neutralization of intracellular pathways. Both means of inhibition have proven benefits in the prevention and resolution of atherothrombotic events. With regard to intracellular inhibition, phosphodiesterases (PDEs) are fundamental for platelet function. Platelets possess several PDEs (PDE2, PDE3 and PDE5) that catalyze the hydrolysis of cyclic adenosine 3'-5'-monophosphate (cAMP) and cyclic guanosine 3'-5'-monophosphate (cGMP), thereby limiting the levels of intracellular nucleotides. PDE inhibitors, such as cilostazol and dipyridamole, dampen platelet function by increasing cAMP and cGMP levels. This review focuses on the roles of PDE inhibitors in modulating platelet function, with particular attention paid to drugs that have anti-platelet clinical indications.
The Molecular Medicine Program and Department of Internal Medicine, University of Utah, Salt Lake City, UT 84112, USA.
Matthew T
MT
Rondina
Andrew S
AS
Weyrich
D000818:Animals; D001792:Blood Platelets / Q000201:enzymology; D000077407:Cilostazol; D004176:Dipyridamole / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use
D010726:Phosphodiesterase Inhibitors; D010975:Platelet Aggregation Inhibitors; D013777:Tetrazoles; D004176:Dipyridamole; D000077407:Cilostazol