Inositol Lipid Metabolism, the Cytoskeleton, Glycoprotein IIb IIIa and Platelets

Abstract

Blood platelets, like many other cells respond to a wide range of agonists by modifications of their lipid metabolism (Lloyd et al., 1973; Lloyd and Mustard, 1974; Mauro et al., 1978, 1983, 1984; Billah and Lapetina 1982a,b; Agranoff et al., 1983; Broekman et al.,1981 etc...) including a transient fall in [³²P]PtdIns4,5P ₂ (1) labelling, increases in diacylglycerol (DAG) production (Rittenhouse-Simmons, 1979; Mauro et al., 1984) and phosphatidic acid (PtdOH) and at later times increases in the mass of Ptdlns4,5P ₂ (Perret et al., 1983). However these lipid modifications are not alone and a full range of metabolic responses have been reported, including GTP binding to a full set of G-proteins, serine/threonine phosphorylations via Ca²⁺/саlmodulin-, cyclic AMP-dependent protein kinases or protein kinases C, tyrosine protein phosphorylations. The cellular responses are also extremely diverse, ranging from cytoplasm i.e. pH changes and free calcium concentration increases to cytoskeletal modifications and secretion. Although many of the cellular events have been studied up to the end of aggregation (i.e. 1 to 5 minutes after stimulation), it is important to keep in mind that the aggregated platelets are still able to react to stimulating agonists (ADP, TXA₂ adrenaline etc...) or physiological antagonists (PGI₂...) as shown by experiments on the platelet-strip (Salganicoff et al., 1983). For instance, in vivo, the contractile properties are responsible for bringing together the lips of a wound.