Regulation of intracellular cAMP in platelets by thrombin. Thrombin restricts intracellular cAMP content by suppression of synthesis from ATP and acceleration of hydrolysis of cAMP to 5′AMP by PDE3A. After activation of PAR-1, thrombin inhibits adenylate cyclase either through PAR1-coupled G_i protein directly, through G_q protein directly, or through G_q protein-induced of ADP from dense granules via the PLCβ pathway. In the latter, secreted ADP binds to the outside surface P2Y₁₂ receptor, which is coupled to G_i2 to inhibit adenylate cyclase. Furthermore, thrombin via PAR-1 links to G_q, stimulates PI3K and PDK1, which in turn phosphorylates Akt, which in turn phosphorylates PDE3A. Elevation of PDE3A lowers intracellular cAMP content.