Cardiovascular Division, King's College London, School of Medicine, Franklin-Wilkins Building, Stamford Street, London, UK.
Microcirculation. 2010 Jan;17(1):39-46. doi: 10.1111/j.1549-8719.2010.00001.x.
Lysophosphatidic acid (LPA) increases permeability of cerebral endothelium in culture, but it has been suggested that histamine release is required in vivo.
Cerebral venular permeability was measured by using the single-vessel micro-occlusion technique, and fura-2 ratios were used to track changes in endothelial [Ca(2+)].
Topical acute LPA application dose-dependently increased permeability (log EC(50)-9.4; similar to the K(d) of the LPA1 receptor). The calcium response to LPA was similar to histamine, but the permeability response was unaffected by H(2)-histamine receptor antagonism, and was blocked by Ki16425, a LPA1 receptor antagonist. The permeability response was blocked by nitric oxide synthase and free radical scavenging, which were carried out together, but not separately. Intravascular LPA bolus injection increased permeability. Whole serum albumin, or plasma albumin co-applied with LPA, increased permeability, but less potently than LPA itself (log EC(50) 5.1 and 6.1, respectively). Tachyphylaxis of the LPA1 receptor was demonstrated by LPA application for 10 minutes, which resulted in suppression of the response to subsequent applications for the following 15 minutes.
Lysophosphatidic acid increases cerebrovascular permeability by acting directly on the endothelium and utilizes both nitric oxide and free radical signaling pathways.
溶血磷脂酸（LPA）增加培养中的脑内皮通透性，但有人认为组胺释放是必需的。
采用单血管微闭塞技术测量脑静脉通透性，并使用 fura-2 比率跟踪内皮细胞[Ca(2+)]的变化。
局部急性 LPA 应用呈剂量依赖性增加通透性（log EC(50)-9.4；与 LPA1 受体的 K(d)相似）。LPA 引起的钙反应与组胺相似，但通透性反应不受 H(2)-组胺受体拮抗作用的影响，并且被 LPA1 受体拮抗剂 Ki16425 阻断。一氧化氮合酶和自由基清除剂共同作用阻断了通透性反应，但单独作用则没有效果。血管内 LPA 脉冲注射增加了通透性。全血清白蛋白或与 LPA 共同应用的血浆白蛋白增加了通透性，但作用不及 LPA 本身强（log EC(50)分别为 5.1 和 6.1）。LPA 应用 10 分钟可导致 LPA1 受体脱敏，导致随后 15 分钟内对后续应用的反应受到抑制。
溶血磷脂酸通过直接作用于内皮细胞增加脑血管通透性，并利用一氧化氮和自由基信号通路。
