Regulation of Platelet Activation By cAMP and cGMP

All agonist-induced platelet responses, including shape change, aggregation, adhesion and secretion are inhibited by increased intracellular cAMP levels (1). Synthesis of cAMP in the platelet is stimulated by the binding of mediators, such as prostacyclin and adenosine, to cell surfece receptors ( ) coupled to GTP binding proteins (Fig. 1). 

Each mily is further divided into subclasses which, in the conserved domain, demonstrate up to 70-90% identity to each other within a mily and are encoded by distinct but homologous genes, hr addition, many of these subclass proteins have sever members which are products of alternative mRNA splicing. 

Hidaka and Asano reported in 1976 the isolation of three distinct cyclic nucleotide PDEs by DEAE-cellulose chromatography firom the soluble Suction of platelet extracts (9). llrese three forms were affected differently by various PDE inhibitors (10,11) and also demonstrated distinct biochemical properties. Form I had a high Km for cAMP and a low Km for cGMP, and is now known as the cGMP-binding cGMP-specific PDE (cGB-PDE or PDE 5). The other two forms are specific for cAMP and are known as the 

Short Name Family of Gene Products Family- Specific Inhibitors cAMP (mM) cGMP (mM) 

PDEl Ca++- Calmodulin -dependent (CM-PDE) 3 Vinpocetin, phenothia -zincs 50 35 

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