PGI2 binding to the associated IP receptor (coupled to Gs) leads to an activation of the AC and thus to an increase of intracellular cAMP. Its elevation downregulates store-mediated calcium entry, calcium mobilization and secretion, as well as platelet adhesion to subendothelial collagen via integrin α2β1. The cAMP increase further results in an activation of protein kinase-A (PKA) and in principle, in an inhibition of platelet activation. Analogous to cAMP, PKA activity has been associated with a reduced Ca2+ release from intra-platelet stores