Deficiency of Src homology 2 domain-containing inositol 5-phosphatase 1 affects platelet responses and thrombus growth.

Platelets are critical for normal hemostasis. Their deregulation can lead to bleeding or to arterial thrombosis, a primary cause of heart attack and ischemic stroke. Src homology 2 domain-containing inositol 5-phosphatase 1 (SHIP1) is a 5-phosphatase capable of dephosphorylating the phosphatidylinositol 3,4,5-trisphosphate second messenger into phosphatidylinositol 3,4-bisphosphate.

Importance of platelet phospholipase Cgamma2 signaling in arterial thrombosis as a function of lesion severity.

Objective: Platelet activation occurs in response to adhesion receptors for von Willebrand factor (GPIb-V-IX) and collagen (GPVI and alpha2beta1 integrin) acting upstream of phospholipase C (PLC) gamma2. However, PLCbeta transduces signals from Galphaq protein-coupled receptors for soluble agonists (P2y1, TxA2/TP, and thrombin/PAR). A Gi-dependent pathway amplifies most of these responses.

A role of the fast ATP-gated P2X1 cation channel in thrombosis of small arteries in vivo.

The P2X1 receptor is a fast ATP-gated cation channel expressed in blood platelets, where its role has been difficult to assess due to its rapid desensitization and the lack of pharmacological tools. In this paper, we have used P2X1-/- and wild-type mouse platelets, treated with apyrase to prevent desensitization, to demonstrate the function of P2X1 in the response to thrombogenic stimuli. In vitro, the collagen-induced aggregation and secretion of P2X1-deficient platelets was decreased, as was adhesion and thrombus growth on a collagen-coated surface, particularly when the wall shear rate was elevated.