How does adenosine diphosphate (ADP) activate platelets Essay

How does adenosine diphosphate (ADP) activate platelets - Essay Example ADP induces platelet shape change, calcium flux, and inhibition of adenylyl cyclase, leading to aggregation. Kahner et al. (2006) also stated that rapid shape change, release of granular contents, generation of lipid mediators, and aggregation occur during platelet activation. Various surface receptors involved in platelet activation include G protein coupled receptors (GPCRs), integrins and glycoprotein receptors. Adenosine diphosphate (ADP) (released from platelet granules) and thromboxane A2 (generated within platelets) are the secondary mediators that activate other resting platelets, resulting in the amplification of initial physiological haemostatic response. Adenosine nucleotides are released following platelet activation signal through the P2 purinergic receptors on the platelet membrane. The two types of P2 receptors are ligand-gated cation channels (P2X), or GPCRs (P2Y). Till date, seven different P2X receptors (P2X1)) and eight distinct P2Y receptors (P2Y1,2,4,6,11-14) hav e been identified which were cloned from mammalian tissues. P2Y1, P2Y12, andP2X1 subtypes are the P2 purinergic receptors expressed on platelets and their physiologic agonists are ADP, ADP, and adenosine triphosphate (ATP), respectively. These receptors, when activated by the agonists, initiate a complex signaling cascade that ultimately results in platelet activation and thrombus formation. The physiological agonist for the P2Y1 receptor is ADP. This receptor can also be stimulated in vitro by 2MeSADP, ADP, APDaS and ADPbS in the decreasing order of potency and is involved platelet shape change and aggregation brought about by ADP. P2Y12 is coupled to Gi2 protein. Upon stimulation, the Ga and Gbc subunits of the heterotrimeric G protein dissociate and activate various signaling pathways. The Gai2 is found to be responsible for ADP-mediated inhibition of adenylyl cyclase and subsequent reduction in cytosolic cAMP concentrations. This is one