Molecular events in ADP-induced platelet shape change

Adenosine 5'-diphosphate (ADP) causes platelets to change shape from discs to spiculated spheres. The molecular events in this response are beginning to unravel. The platelet P2T receptor is resolved into three P2 receptor subtypes: P2Y(1), P2X(1) and P2T(AC). The ADP-induced platelet shape change is mediated by the P2Y(1) receptor without any significant contribution from the other two P2 receptor subtypes, P2Y(1) receptor stimulation results in coupling to G(q). and activation of phospholipase C. The intracellular calcium increases associated with the P2Y(1) receptor lead to platelet shape change through stimulation of calcium-calmodulin kinase and myosin light-chain kinase. Recent studies have provided evidence for a calcium-independent pathway leading to platelet shape change. This calcium-insensitive pathway is mediated by activation of RhoA and a Rho kinase, p160ROCK. Thromboxane A(2) stimulates the p160ROCK pathway through coupling to Glu(12/13). It remains to be seen whether the P2Y(1) receptor also couples to G(12/13). (C) 1999 Prous Science. All rights reserved.