Presence in normal human urine of a hypotensive and platelet-activating phospholipid.

Presence in normal human urine of a hypotensive and platelet-activating phospholipid.
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正常人尿液中存在降血压和血小板活化磷脂。

DOI:
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发表时间:
1983
影响因子:
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通讯作者:
L. Hernando
L. Hernando
中科院分区:
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文献类型:
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作者:
M. Sánchez;P. Iñarrea;V. Alvarez;F. Alonso;J. Egido;L. Hernando

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将来自正常血压志愿者和系统性红斑狼疮肾小球肾病患者的尿液依次通过负压超滤浓缩,对蒸馏水透析,并提取到有机溶剂混合物(氯仿:甲醇:水,1:1:0.9 vol/vol)的氯仿相中。脂质部分通过薄层色谱法在硅胶板上使用中性、酸性和碱性有机溶剂混合物进一步纯化,然后测试其诱导兔血小板释放[3 H]血清素的能力。根据其色谱行为、对10(-6)M吲哚美辛预处理血小板的抗性以及碱性甲醇分解或磷脂酶A2、C和D处理的活性损失,所有样品均含有与合成血小板活化因子(PAF-乙酸酯)相似的血小板活化部分。合成PAF-乙酸酯和尿因子之间的交叉脱敏实验表明,这两种化合物通过激活相同的假定受体作用于血小板。此外,当动脉内注射正常血压大鼠时,尿因子引起低血压,并且这种活性也被碱性甲醇分解废除。总之,这些数据提供了正常人尿液中存在的证据,并且可能是肾脏释放的具有血小板活化和膨胀活性的脂质因子的证据,该脂质因子的一般结构似乎是烷基-酰基-甘油基-磷酸胆碱,因此,与炎症介质PAF-乙酸酯和抗高血压极性肾髓质脂质的结构相似。
Urine from normotensive volunteers and patients with systemic lupus erythematosus glomerulonephropathy was sequentially concentrated by negative-pressure ultrafiltration, dialyzed against distilled water, and extracted into the chloroform phase of a mixture of organic solvents(chloroform:methanol:water, 1:1:0.9 vol/vol). The lipid fraction was further purified by thin-layer chromatography on silica gel plates using neutral, acidic, and basic mixtures of organic solvents and it was then tested for its ability to induce the release of [3H]serotonin from rabbit platelets. All of the samples contained a platelet-activating moiety similar to a synthetic platelet-activating factor (PAF-acether) on the basis of its chromatographic behavior, resistance to the pretreatment of platelets by 10(-6) M indomethacin, and loss of activity by alkaline methanolysis or treatment by phospholipases A2, C, and D. Cross-densensitization experiments between synthetic PAF-acether and the urine factor showed that both compounds act on platelets through the activation of the same putative receptor. Further, the urine factor induced hypotension when intra-arterially injected in normotensive rats, and this activity was also abrogated by alkaline methanolysis. In summary, these data provide evidence of the presence in normal human urine and, probably, of the release by the kidney of a lipid factor with platelet-activating and hypotensive activity whose general structure seems to be alkyl-acyl-glyceryl-phosphorylcholine and, therefore, is similar to the structure of the inflammatory mediator PAF-acether and the antihypertensive polar renomedullary lipid.