Platelet activation by thrombin

When an agonist binds to a specific receptor on the platelet membrane a series of morphological and metabolic changes begin which induces the shape change, aggregation and granule release. thrombin multifunctional serinoprotease and a strong platelet agonist, has two different types of binding sites on platelets membranes: high and moderate affinity. The last one belongs to the beta(2) adrenergic receptors with the seven transmembrane domains coupled to specific G proteins, which triggers the metabolic pathways with specific enzymes. Phospholipase C beta activity forms two seconds messengers: Inositol 3 phosphate that induces calcio release from dense tubular system to the citosol, and the diacylglicerol which actives protein quinase C. The platelets do not proliferate but it have been found in the enzymes related to oncogenes. Tyrosine kinase family, related to cellular proliferation and oncogenes phosphorilate tyrosine residues belong mostly to the citosolic non receptor group, as Scr, Syk and FAK Pi P2 hydrolysis results also from the stimulation of PLC gamma which is independent of G proteins. Thrombin induces the formation of the trimeric complex consisting in phospholypase C gamma Pas GAP and Rap Ib, bringing phospholypase C gamma in contact with membrane phosphoinositides. Phosphoinositol 3 kinase catalysates phosphorilation of 3 inositol phospholipids on the 3 position of the inositol ring forming new phosphoinositol products. The identification of thrombin receptors in platelets give us the opportunity to contemplate the development of a new class of agents that will selectively inhibit the effects of thrombin on cells.