The platelet as a Ca (2+) -driven cell: mechanisms which may modulate Ca (2+) -driven responses
Scrutton, M.C.
Advances in Experimental Medicine and Biology 344: 1-15
1993
ISSN/ISBN: 0065-2598 PMID: 8209779 Document Number: 419644
Platelets play a central role in the haemostatic response (Gordon and Milner, 1976). They also contribute significantly to the initiation of responses by other cells which occur concomitantly with, or as a necessary sequel to, the initial events that prevent loss of blood (Larsen et al, 1989). Some of the excitatory agonists involved in initiating these responses, and the nature of the responses which can occur, are shown in Fig. 1. The response pattern is characteristic of the agonist used (Crawford and Scrutton, 1987), and in Fig. 1 the excitatory agonists are grouped according to the type of response pattern which they induce. These response patterns can be summarised as follows:1"Direct". In this pattern which for human platelets is induced by thrombin and PAF, and possibly in some instances by vasopressin, all responses can result directly from the initial agonist-receptor interaction. The responses induced are aggregation, thromboxane A2 synthesis and secretion from all three storage granules (amine storage, protein storage and lysosomes) present in the platelet (Crawford and Scrutton, 1987). Interplay between the effect of the released products, particularly Adp and thromboxane A2, leads to enhanced aggregation especially when a low concentration of the initial agonist is used (Packham and Mustard, 1986). 2"Adhesion-dependent". This pattern is characteristic of collagen. It is initiated by interaction of platelets with, and their spreading on, collagen fibrils which causes thromboxane A2 synthesis, secretion from all three storage granules and uniquely an increase in the phosphatidylserine content of the outer leaflet of the plasma membrane. The enhanced extracellular exposure of phosphatidylserine provides the trigger for the assembly of the factor X and prothrombin activation complexes on the activated platelets and so localises thrombin formation to the vicinity of the site of collagen exposure (Revers et al, permeabilised preparations occur at high concentrations of this cyclic nucleotide (Haslam et al 1985) and appear unlikely to be of physiological significance.