Effect of glycine on the calcium signal of thrombin-stimulated platelets

Abstract

In treatment of hemorrhagic shock, small-volume infusion of 7.5% NaCl gives immediate hemodynamic improvement, but in vitro experiments suggest it depresses the hemostatic system. Since previous reports showed that hyperosmotic glycine solutions preserved the platelet function better than hyperosmotic NaCl solutions, we investigated whether glycine changes the intracellular calcium ([Ca]i) signal. Platelets were incubated in hyperosmotic solutions containing sodium glycine or glycine base and stimulated with 0.1 IU/ml thrombin. [Ca]i increases were compared with an isosmotic control. Platelets incubated in zero calcium/EGTA were used to study separately the effect of glycine on calcium mobilization from intracellular stores and extracellular calcium entry. When NaCl was replaced by sodium glycine, the [Ca]i increase produced by thrombin was enhanced, because the calcium entry increased without changes in the mobilization of stored calcium. The addition of 50 mmol/l glycine base to the HEPES-buffered media increases the thrombin-induced entry of calcium or manganese. This study demonstrates that hyperosmotic glycine solutions increase the entry of calcium. This effect contrasts with the impairment of the thrombin-induced calcium signals by NaCl. The addition of low amounts of glycine in resuscitation solutions would be useful to reduce dysfunctional inflammatory responses without the risk of bleeding; however, concentrated solutions could cause toxic effects.

Critical Role for CD38-mediated Ca2+ Signaling in Thrombin-induced Procoagulant Activity of Mouse Platelets and Hemostasis

“…PKC isoforms variably regulate platelet Ca 2ϩ signals and have influences on PS exposure (19,25,26). Furthermore, different stimulants of platelets play variable roles in PS exposure; for instance, collagen results in increased PS exposure, whereas thrombin as a co-agonist additionally contributes to PS exposure (27)(28)(29)(30) whereas thrombin very efficiently mobilizes intracellular Ca 2ϩ from internal stores (33)(34)(35), and therefore, PS exposure is additionally enhanced with thrombin. Human platelets possess two intracellular Ca 2ϩ stores (1,36).…”