STEREOSELECTIVE EFFECTS OF LYSOPHOSPHATIDYLSERINE IN RODENTS
STEREOSELECTIVE EFFECTS OF LYSOPHOSPHATIDYLSERINE IN RODENTS
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DOI：
10.1111/j.1476-5381.1988.tb10322.x
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发表时间：
1988-03-01
影响因子：
7.3
通讯作者：
TOFFANO, G
中科院分区：
文献类型：
--
作者：
CHANG, HW;INOUE, K;TOFFANO, G
1溶血磷脂酰丝氨酸的L-对映体和d -对映体的药理作用已在小鼠体内通过跟踪该磷脂引起的血液和脑葡萄糖含量的增加进行了研究。初步实验证实，这些影响是溶血磷脂酰丝氨酸诱导的肥大细胞活化的结果，因为在携带W/Wv基因型的肥大细胞缺陷小鼠中没有观察到这些影响。2最大的高血糖反应和脑葡萄糖积累发生在10mg kg-1溶血磷脂酰丝氨酸（静脉注射）。半最大效应为3.5 mg kg-1。溶血磷脂酰- d -丝氨酸在高达25mg kg-1的剂量下，可引起最大效果的40%（血糖）和60%（脑葡萄糖）。两种对映体之间的活性差异也观察到当这种磷脂通过口服途径给药时对溶血磷脂酰丝氨酸的脱敏。溶血磷脂酰- l-丝氨酸在小鼠腹膜肥大细胞中比d -对映体更活跃。在20%到50%的组胺释放之间观察到10的活性比。在大鼠腹膜肥大细胞中也得到了类似的结果。综上所述，丝氨酸α碳原子的构型影响溶血磷脂酰丝氨酸在体内和体外的活性。因此，丝氨酸氨基的适当位置是磷脂头基团与肥大细胞膜中受体最佳相互作用所必需的。
1 The pharmacological action of the L- and D-enantiomers of lysophosphatidylserine has been studied in vivo by following the increase in blood and brain glucose content caused by this phospholipid in mice. Preliminary experiments have confirmed that these effects are the consequence of lysophosphatidylserine-induced mast cell activation since they are not observed in mastcell- deficient mice bearing the W/Wv genotype. 2 Maximal hyperglycaemic response and brain glucose accumulation occur at 10 mg kg-1 lysophosphatidyl-L-serine (i.v.). Half-maximal effect is at 3.5 mg kg-1. Lysophosphatidyl-D-serine at doses of up to 25 mg kg-1 i.v. elicits 40% (blood glucose) and 60% (brain glucose) of the maximal effect. The difference in activity between the two enantiomers is also observed in the desensitization to lysophosphatidylserine occurring when this phospholipid is administered by the oral route. 3 Lysophosphatidyl-L-serine is more active than the D-enantiomer in mouse isolated peritoneal mast cells. Activity ratios of 10 are observed between 20 and 50% histamine release. Similar results are obtained with rat isolated peritoneal mast cells. 4 It is concluded that the configuration of the alpha carbon atom of serine influences the activity of lysophosphatidylserine in vivo and in vitro. Thus, the appropriate position of the serine amino group is required for optimal interaction of the phospholipid head group and a receptor in the mast cell membrane.