Walter Ulrich, Gambaryan Stepan
Institute of Clinical Biochemistry and Pathobiochemistry, University of Wuerzburg, Josef-Schneider-Str. 2, Wuerzburg, 97080, Germany.
Handb Exp Pharmacol. 2009(191):533-48. doi: 10.1007/978-3-540-68964-5_23.
Platelets are specialized adhesive cells that play a key role in normal and pathological hemostasis through their ability to rapidly adhere to subendothelial matrix proteins (platelet adhesion) and to other activated platelets (platelet aggregation). NO plays a crucial role in preventing platelet adhesion and aggregation. In platelets, cGMP synthesis is catalyzed by sGC, whereas PDE2, PDE3 and PDE5 are responsible for cGMP degradation. Stimulation of cGK by cGMP leads to phosphorylation of multiple target substrates. These substrates inhibit elevation of intracellular calcium, integrin activation, cytoskeletal reorganization, and platelet granule secretion, events normally associated with platelet activation. The NO/cGMP pathway also plays a significant role in many other blood cell types in addition to platelets. In leukocytes, depending on the specific cell type, cGMP signaling regulates gene expression, differentiation, migration, cytokine production, and apoptosis.
血小板是特殊的黏附细胞，通过其快速黏附于内皮下基质蛋白（血小板黏附）以及其他活化血小板（血小板聚集）的能力，在正常和病理性止血过程中发挥关键作用。一氧化氮（NO）在防止血小板黏附和聚集方面起着至关重要的作用。在血小板中，可溶性鸟苷酸环化酶（sGC）催化环磷酸鸟苷（cGMP）的合成，而磷酸二酯酶2（PDE2）、磷酸二酯酶3（PDE3）和磷酸二酯酶5（PDE5）则负责cGMP的降解。cGMP对蛋白激酶G（cGK）的刺激导致多种靶底物的磷酸化。这些底物抑制细胞内钙升高、整合素激活、细胞骨架重组以及血小板颗粒分泌，这些事件通常与血小板激活相关。除血小板外，NO/cGMP途径在许多其他血细胞类型中也发挥着重要作用。在白细胞中，根据特定细胞类型，cGMP信号传导调节基因表达、分化、迁移、细胞因子产生和细胞凋亡。
