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人胚胎源性血小板活化因子的生化与药理学特性

Biochemical and pharmacological characterization of human embryo-derived platelet activating factor.

作者信息

Collier M, O'Neill C, Ammit A J, Saunders D M

机构信息

Human Reproduction Unit, Royal North Shore Hospital, St Leonards, NSW, Australia.

出版信息

Hum Reprod. 1988 Nov;3(8):993-8. doi: 10.1093/oxfordjournals.humrep.a136830.

Abstract

The soluble platelet activating factor (PAF) produced by mouse embryos was shown to have properties similar to 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphocholine (PAF-acether). In this study PAF was extracted from the medium in which human embryos were cultured for approximately 18 h prior to transfer. The extracted embryo-derived PAF moved on silica thin layer chromatograms with the same RF of 0.26 +/- 0.03 (n = 26) as PAF-acether. Embryo-derived PAF or PAF-acether activity was assayed by monitoring the decrease in the proportion of single platelets in rabbit whole blood due to aggregation on incubation at 37 degrees C. The two agonists were said to be of the same activity, if they induced the same degree of platelet aggregation after 15 min incubation. PAF-acether (93 nM) and embryo-derived PAF of similar activity induced an identical time response of platelet aggregation, the response being maximal by 6 min. PAF-acether, over the range 5.6-200 nM, induced a decrease that was linear when plotted on a log-log scale. Embryo-derived PAF and PAF-acether (184 nM) gave identical dose responses when serially diluted to 16 nM. Pharmacologically, the action of embryo-derived PAF and PAF-acether (46 nM) on platelet aggregation was significantly inhibited by 3.75 microM of the PAF-specific receptor inhibitor, SRI 63-441, and completely inhibited at 15 microM SRI 63-441. Embryo-derived PAF and PAF-acether (184 nM) were inactivated to the same degree by incubation with 5-13 IU/ml phospholipase A2 (pA2).(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

小鼠胚胎产生的可溶性血小板活化因子(PAF)被证明具有与1-O-烷基-2-乙酰基-sn-甘油-3-磷酸胆碱(PAF-乙醚)相似的特性。在本研究中,PAF是从人胚胎移植前培养约18小时的培养基中提取的。提取的胚胎源性PAF在硅胶薄层色谱图上移动,其比移值(RF)与PAF-乙醚相同,为0.26±0.03(n = 26)。通过监测兔全血中单个血小板比例因在37℃孵育时聚集而减少的情况,来测定胚胎源性PAF或PAF-乙醚活性。如果两种激动剂在孵育15分钟后诱导相同程度的血小板聚集,则称它们具有相同的活性。PAF-乙醚(93 nM)和活性相似的胚胎源性PAF诱导相同的血小板聚集时间反应,该反应在6分钟时达到最大值。在5.6 - 200 nM范围内,PAF-乙醚诱导的减少在对数-对数尺度上绘制时呈线性。当连续稀释至16 nM时,胚胎源性PAF和PAF-乙醚(184 nM)给出相同的剂量反应。在药理学上,3.75 microM的PAF特异性受体抑制剂SRI 63 - 441可显著抑制胚胎源性PAF和PAF-乙醚(46 nM)对血小板聚集的作用,在15 microM SRI 63 - 441时完全抑制。胚胎源性PAF和PAF-乙醚(184 nM)与5 - 13 IU/ml磷脂酶A2(pA2)孵育后失活程度相同。(摘要截短于250字)

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