去氨加压素在体外刺激人血小板p -选择素的表达。

T Wun, T G Paglieroni, N A Lachant
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摘要

去氨加压素(1-去氨氨基-8- d -精氨酸加压素(DDAVP))是精氨酸加压素(AVP)的合成类似物,可用于治疗一些出血性疾病。血小板功能障碍患者改善止血的机制尚不清楚。35名正常受试者的富血小板血浆样本在连续稀释DDAVP、AVP和二磷酸腺苷的条件下孵育。采用荧光标记单克隆抗体和流式细胞术检测血小板活化依赖性抗原CD62 (p -选择素)的表达。1.0 ~ 1000 nmol/L浓度的DDAVP可刺激正常血小板上CD62的显著表达。在DDAVP药理学浓度(1 nmol/L)下,14.1%(0.6% ~ 45.4%)的血小板表达CD62(中位数和范围)。ddavp诱导的CD62表达与avp诱导的CD62表达之间有很强的相关性(rs = 0.62, p = 0.0008),但ddavp诱导的CD62表达与adp诱导的CD62表达之间没有相关性,提示其可能存在V1受体介导的机制。血小板与抗利尿激素V1受体拮抗剂的预孵育完全抑制CD62的表达,以响应DDAVP。我们得出结论,在体外,DDAVP通过与血小板V1受体相互作用直接激活血小板。这一发现可以部分解释davp在体内对止血的作用。
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Desmopressin stimulates the expression of P-selectin on human platelets in vitro.

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.

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