Effect of glycine on the calcium signal of thrombin-stimulated platelets.
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.
Giambelluca
Miriam S
MS
Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, 60 y 120, 1900 La Plata, Argentina.
Gende
Oscar A
OA
D015220:Calcium Channels / Q000187:drug effects*; D020013:Calcium Signaling / Q000502:physiology*; D003600:Cytosol / Q000502:physiology; D005998:Glycine / Q000494:pharmacology*; D018684:Glycine Agents / Q000494:pharmacology*; D006801:Humans; D006982:Hypertonic Solutions / Q000494:pharmacology; D008345:Manganese / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects*; D013917:Thrombin / Q000502:physiology
D015220:Calcium Channels; D018684:Glycine Agents; D006982:Hypertonic Solutions; D008345:Manganese; D013917:Thrombin; D005998:Glycine