Wun T, Paglieroni T G, Lachant N A
University of California Davis Cancer Center, UC Davis School of Medicine, Sacramento 95817, USA.
J Lab Clin Med. 1995 Oct;126(4):401-9.
Desmopressin (1-desamino-8-D-arginine vasopressin (DDAVP)) is a synthetic analog of arginine vasopressin (AVP) and is useful in the treatment of some bleeding disorders. The mechanism of improved hemostasis in patients with platelet dysfunction is uncertain. Platelet-rich plasma samples from 35 normal subjects were incubated with serial dilutions of DDAVP, AVP, and adenosine diphosphate. The expression of the platelet activation-dependent antigen CD62 (P-selectin) was measured by fluorescent-labeled monoclonal antibody and flow cytometry. DDAVP at concentrations of 1.0 to 1000 nmol/L stimulated significant expression of CD62 on normal platelets in vitro. At a pharmacologic concentration of DDAVP (1 nmol/L), 14.1% (0.6% to 45.4%) (median and range) of platelets expressed CD62. There was a strong correlation between DDAVP-induced and AVP-induced CD62 expression (rs = 0.62, p = 0.0008) but not between DDAVP-induced and ADP-induced expression, suggesting a V1 receptor-mediated mechanism. Preincubation of platelets with a vasopressin V1 receptor antagonist completely inhibited CD62 expression in response to DDAVP. We conclude that DDAVP directly activates platelets by interaction with the platelet V1 receptor in vitro. This finding may partially explain in vivo effects of DDAVP on hemostasis.
去氨加压素（1-去氨基-8-D-精氨酸血管加压素（DDAVP））是精氨酸血管加压素（AVP）的合成类似物，可用于治疗某些出血性疾病。血小板功能障碍患者止血改善的机制尚不清楚。将35名正常受试者的富血小板血浆样本与DDAVP、AVP和二磷酸腺苷的系列稀释液孵育。通过荧光标记的单克隆抗体和流式细胞术测量血小板活化依赖性抗原CD62（P-选择素）的表达。浓度为1.0至1000 nmol/L的DDAVP在体外刺激正常血小板上CD62的显著表达。在DDAVP的药理浓度（1 nmol/L）下，14.1%（0.6%至45.4%）（中位数和范围）的血小板表达CD62。DDAVP诱导的和AVP诱导的CD62表达之间存在强相关性（rs = 0.62，p = 0.0008），但DDAVP诱导的和ADP诱导的表达之间不存在相关性，提示V1受体介导的机制。用血管加压素V1受体拮抗剂预孵育血小板可完全抑制对DDAVP的CD62表达。我们得出结论，DDAVP在体外通过与血小板V1受体相互作用直接激活血小板。这一发现可能部分解释了DDAVP在体内对止血的作用。
