Holmsen H
Department of Biochemistry and Molecular Biology, University of Bergen, Norway.
Eur J Clin Invest. 1994 Feb;24 Suppl 1:3-8. doi: 10.1111/j.1365-2362.1994.tb02418.x.
Platelets respond through discrete receptors to a number of physiological agonists and foreign surfaces with a sequence of measurable responses: shape change, aggregation, secretion and arachidonate liberation. Three secretory responses are distinguished: exocytosis of substances from (1) dense granules, (2) alpha-granules and (3) lysosomes. Free arachidonate, liberated from phospholipids by phospholipase A2, is rapidly converted (by oxygenation) to prostaglandins and thromboxanes which, together with secreted ADP and close cell contact, will cause further platelet activation through 'positive feedback' (autocrine stimulation). Some agonists are classified as 'weak' (ADP, vasopressin, platelet-activating factor [PAF], serotonin) because they depend on autocrine stimulation to promote the full sequence of responses, while others are 'strong' agonists (thrombin, collagen) and activate all responses directly without autocrine stimulation. Adrenaline, long thought to be a platelet agonist per se, most probably acts by amplifying the activation brought about by other, proper, agonists. Such synergistic interaction among agonists is very typical for platelet activation and most likely takes place in vivo. Shape change, aggregation and secretion(s) may be tested by flow cytometry or electron microscopy in vitro under conditions that probably reflect the in vivo situation. However, the aggregation response to weak agonists in vitro is dependent on the extracellular [Ca2+], with biphasic aggregation at the low [Ca2+] present when citrate is used as anticoagulant (or in suspension of washed platelets) but not at the physiological [Ca2+] present in platelet-rich plasma from heparinized blood.
血小板通过离散的受体对多种生理激动剂和外来表面做出反应，产生一系列可测量的反应：形状改变、聚集、分泌和花生四烯酸释放。可区分出三种分泌反应：物质从（1）致密颗粒、（2）α颗粒和（3）溶酶体的胞吐作用。由磷脂酶A2从磷脂中释放的游离花生四烯酸迅速（通过氧化）转化为前列腺素和血栓烷，它们与分泌的ADP以及紧密的细胞接触一起，将通过“正反馈”（自分泌刺激）导致进一步的血小板活化。一些激动剂被归类为“弱”激动剂（ADP、血管加压素、血小板活化因子[PAF]、5-羟色胺），因为它们依赖自分泌刺激来促进完整的反应序列，而其他激动剂是“强”激动剂（凝血酶、胶原蛋白），可直接激活所有反应而无需自分泌刺激。长期以来一直被认为本身是血小板激动剂的肾上腺素，很可能通过放大其他合适激动剂引起的活化作用来发挥作用。激动剂之间的这种协同相互作用在血小板活化中非常典型，很可能在体内发生。形状改变、聚集和分泌可以在体外通过流式细胞术或电子显微镜在可能反映体内情况的条件下进行检测。然而，体外对弱激动剂的聚集反应取决于细胞外[Ca2+]，当使用柠檬酸盐作为抗凝剂时（或在洗涤血小板悬液中），在低[Ca2+]时会出现双相聚集，但在来自肝素化血液的富含血小板血浆中存在的生理[Ca2+]时则不会。
