Intracellular calcium mobilization is triggered by clustering of membrane glycoproteins in concanavalin A-stimulated platelets
✍ Scribed by Giuseppe Ramaschi; Mauro Torti; Fabiola Sinigaglia; Cesare Balduini
- Publisher
- John Wiley and Sons
- Year
- 1993
- Tongue
- English
- Weight
- 818 KB
- Volume
- 11
- Category
- Article
- ISSN
- 0263-6484
No coin nor oath required. For personal study only.
✦ Synopsis
Stimulation of human platelets with concanavalin A resulted in a significant increase in the concentration of c toplasmic free Ca2+. This effect was due to two different processes: Ca2+ mobilization from internal stores and Ca' influx from the extracellular medium. Kinetic analysis revealed that the release of CaZ+ from internal storage sites occurred sooner than the opening of plasma membrane Ca2+ channels. The ability of concanavalin A to induce a sustained increase in cytoplasmic Ca2+ concentration was antagonized and reversed by methyl a-D-mannopyranoside, demonstrating that it was promoted by the interaction of the lectin with cell surface glycoproteins. Succinyl-concanavalin A, a dimeric derivative of the lectin, that does not promote patching/capping of the receptor, was able to bind to the platelet surface, and antagonized the effects of native concanavalin A. In addition, succinyl-concanavalin A, per se, was unable to induce Ca2+ mobilization in human platelets. Therefore, the action of the native concanavalin A was mediated by receptor clustering events. Concanavalin A mobilized CaZ+ from the same internal stores from which CaZf was mobilized in response to strong platelet agonists, such as thrombin and arachidonic acid. However, while thrombin was ineffective in inducing CaZ+ release after stimulation of platelets with Con A, ConA was able to cause a full discharge of Ca2+ from internal stores even in platelets previously stimulated with thrombin. These results demonstrate for the first time that the clustering of specific membrane glycoproteins can trigger platelet activation. The physiological implications during platelet aggregation are discussed. KEY woaos-Platelets; concanavalin A; membrane glycoproteins; intracellular calcium.