1-O-十六烷基-2-乙酰基-sn-甘油-3-磷酸（N，N，N-三甲基）己醇胺：一种具有部分激动剂活性的血小板活化因子类似物。

1-O-hexadecyl-2-acetyl-sn-glycero-3-phospho (N,N,N trimethyl) hexanolamine: an analogue of platelet-activating factor with partial agonist activity.

作者信息

Grigoriadis G, Stewart A G

机构信息

Department of Physiology, University of Melbourne, Parkville, Victoria, Australia.

出版信息

Br J Pharmacol. 1991 Sep;104(1):171-7. doi: 10.1111/j.1476-5381.1991.tb12403.x.

DOI:10.1111/j.1476-5381.1991.tb12403.x

PMID:1664761

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1908285/

Abstract

During studies of the role of platelet-activating factor (PAF) in macrophage superoxide anion generation (O2(-1], we identified an agonist action of the putative PAF receptor antagonist 1-O-hexadecyl-2-acetyl-sn-glycero-3-phospho (N,N,N-trimethyl) hexanolamine (hexanolamine PAF) in guinea-pig macrophages. The 1-O-octadecyl form of this compound has specific antagonist actions at PAF receptors. 2. The agonist properties of hexanolamine PAF were examined in rabbit washed platelets (aggregation) and in guinea-pig peritoneal macrophages (O2- generation). 3. Hexanolamine PAF induced significant platelet aggregation (50% of the PAF maximum). However, the omission of bovine serum albumin (BSA) from the Tyrode buffer resulted in a diminution of the response of washed platelets during storage for 24 h at 4 degrees C (7% of PAF maximum), whereas the maximum response to PAF was unaffected by storage for this period, irrespective of the presence of BSA. 4. Platelet aggregation induced by hexanolamine PAF was not accompanied by a detectable increase in intracellular calcium [Ca2+]i, whereas the aggregation response to PAF was preceded by a large rise in [Ca2+]i. 5. Hexanolamine PAF induced O2- generation in adherent macrophages, with a maximum response 45% of that to PAF. Hexanolamine PAF (100 nM), at a concentration equi-effective with PAF (1 nM) for stimulation of O2- generation in macrophages, induced an increase in [Ca2+]i which was significantly less than that induced by PAF. 6. PAF concentration-response curves were constructed in platelets or macrophages following pretreatment with hexanolamine PAF (0.1 and 1 microM). The interaction between PAF and the putative partial agonist (hexanolamine PAF) had the characteristics expected of a partial agonist interacting with a full agonist.7. Platelet aggregation induced by hexanolamine PAF was antagonized non-competitively by the PAF receptor antagonist, WEB 2086, whereas antagonism of PAF-induced aggregation by WEB 2086 was competitive. Macrophage 2- generation induced by hexanolamine PAF or PAF was antagonized by WEB 2086.8. These data indicate that hexanolamine PAF is a partial agonist at PAF receptors in macrophages and platelets. The inability of hexanolamine PAF to increase [Ca2+]i in platelets suggests that PAF receptors may be coupled to platelet aggregation by both Ca2 +-dependent and -independent pathways.

摘要

在研究血小板活化因子（PAF）在巨噬细胞超氧阴离子生成（O₂⁻）中的作用时，我们在豚鼠巨噬细胞中鉴定出了假定的PAF受体拮抗剂1 - O - 十六烷基 - 2 - 乙酰 - sn - 甘油 - 3 - 磷酸（N，N，N - 三甲基）己醇胺（己醇胺PAF）的激动剂作用。该化合物的1 - O - 十八烷基形式在PAF受体上具有特异性拮抗剂作用。2. 在兔洗涤血小板（聚集）和豚鼠腹腔巨噬细胞（O₂⁻生成）中检测了己醇胺PAF的激动剂特性。3. 己醇胺PAF诱导显著的血小板聚集（达到PAF最大聚集量的50%）。然而，在Tyrode缓冲液中省略牛血清白蛋白（BSA）会导致洗涤后的血小板在4℃储存24小时期间反应减弱（为PAF最大聚集量的7%），而在此期间PAF的最大反应不受储存影响，无论是否存在BSA。4. 己醇胺PAF诱导的血小板聚集并未伴随细胞内钙[Ca²⁺]i的可检测增加，而对PAF的聚集反应之前[Ca²⁺]i会大幅升高。5. 己醇胺PAF诱导贴壁巨噬细胞产生O₂⁻，最大反应为PAF的45%。在刺激巨噬细胞产生O₂⁻方面，己醇胺PAF（100 nM）的浓度与PAF（1 nM）等效，但其诱导的[Ca²⁺]i增加明显小于PAF诱导的增加。6. 在血小板或巨噬细胞中，用己醇胺PAF（0.1和1 μM）预处理后构建了PAF浓度 - 反应曲线。PAF与假定的部分激动剂（己醇胺PAF）之间的相互作用具有部分激动剂与完全激动剂相互作用的预期特征。7. 己醇胺PAF诱导的血小板聚集被PAF受体拮抗剂WEB 2086非竞争性拮抗，而WEB 2086对PAF诱导的聚集的拮抗是竞争性的。己醇胺PAF或PAF诱导的巨噬细胞O₂⁻生成被WEB 2086拮抗。8. 这些数据表明己醇胺PAF是巨噬细胞和血小板中PAF受体的部分激动剂。己醇胺PAF不能增加血小板中的[Ca²⁺]i，这表明PAF受体可能通过钙依赖性和非依赖性途径与血小板聚集偶联。