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S(+)和R(-)γ-乙烯基-GABA通过人离体灌注胎盘的过程。

Passage of S(+) and R(-) gamma-vinyl-GABA across the human isolated perfused placenta.

作者信息

Challier J C, Rey E, Bintein T, Olive G

机构信息

Biologie de la Reproduction, Université P. & M. Curie, Paris, France.

出版信息

Br J Clin Pharmacol. 1992 Aug;34(2):139-43. doi: 10.1111/j.1365-2125.1992.tb04122.x.

DOI:10.1111/j.1365-2125.1992.tb04122.x
PMID:1419475
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1381530/
Abstract
  1. The maternal to foetal transfers of S(+)- and R(-)-gamma-vinyl-GABA (VGB) across the human isolated perfused placenta were low and comparable with those of acidic alpha-amino acids. 2. The placental uptake of the active S(+)-isomer from the maternal circulation exceeded that of the R(-)-isomer and this was reflected by a corresponding difference in placental tissue concentrations. 3. During perfusion with recirculation of the foetal medium, the two enantiomers were present at a similar concentration and did not concentrate in foetal perfusate, indicating that the excess amount of S(+)-VGB cleared from the maternal circulation was not accessible to the foetal perfusate. Furthermore, stable concentrations of both isomers in the foetal perfusate suggested a lack of placental metabolism. 4. Possible explanations of these findings include the operation of a stereoselective sodium-dependent-GABA placental uptake system on the maternal side, similar to that observed in neuronal tissue, or stereoselective binding to a placental GABA transaminase.
摘要
  1. S(+)-和R(-)-γ-乙烯基-GABA(VGB)经人离体灌注胎盘的母胎转运率较低,与酸性α-氨基酸的转运率相当。2. 母体循环中活性S(+)-异构体的胎盘摄取量超过R(-)-异构体,胎盘组织浓度的相应差异反映了这一点。3. 在胎儿培养基再循环灌注期间,两种对映体的浓度相似,且未在胎儿灌注液中浓缩,这表明从母体循环中清除的过量S(+)-VGB无法进入胎儿灌注液。此外,胎儿灌注液中两种异构体的浓度稳定,提示胎盘缺乏代谢作用。4. 这些发现的可能解释包括在母体一侧存在类似于在神经组织中观察到的立体选择性钠依赖性GABA胎盘摄取系统,或与胎盘GABA转氨酶的立体选择性结合。

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引用本文的文献

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Management of epilepsy during pregnancy.孕期癫痫的管理
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Vigabatrin: placental transfer in vivo and excretion into breast milk of the enantiomers.氨己烯酸:对映体在体内的胎盘转运及向母乳中的排泄。
Br J Clin Pharmacol. 1998 Apr;45(4):409-11. doi: 10.1046/j.1365-2125.1998.t01-1-00693.x.
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Vigabatrin. Clinical pharmacokinetics.
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本文引用的文献

1
Maternofetal transfer of two benzodiazepines. Effect of plasma protein binding and placental uptake.两种苯二氮䓬类药物的母婴转运。血浆蛋白结合和胎盘摄取的影响。
Dev Pharmacol Ther. 1982;4(3-4):158-72. doi: 10.1159/000457405.
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Increased gamma-aminobutyric acid (GABA), homocarnosine and beta-alanine in cerebrospinal fluid of patients treated with gamma-vinyl GABA (4-amino-hex-5-enoic acid).接受γ-乙烯基GABA(4-氨基己-5-烯酸)治疗的患者脑脊液中γ-氨基丁酸(GABA)、高肌肽和β-丙氨酸增加。
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Leucine catabolism in human term placenta.人类足月胎盘的亮氨酸分解代谢
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Kinetics of the sodium-dependent transport of gamma-aminobutyric acid by synaptosomes.突触体对γ-氨基丁酸的钠依赖性转运动力学
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Transfer across the perfused human placenta of antipyrine, sodium and leucine.安替比林、钠和亮氨酸在灌注人胎盘中的转运。
Am J Obstet Gynecol. 1972 Nov 15;114(6):822-8. doi: 10.1016/0002-9378(72)90909-x.
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Amino acid transport in human placental slices.人胎盘切片中的氨基酸转运
Am J Obstet Gynecol. 1974 Dec 15;120(8):1092-8. doi: 10.1016/0002-9378(74)90155-0.
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Kinetics of the enantiomers of vigabatrin after an oral dose of the racemate or the active S-enantiomer.
Clin Pharmacol Ther. 1986 Nov;40(5):581-6. doi: 10.1038/clpt.1986.227.
8
Stereoselective uptake of the GABA-transaminase inhibitors gamma-vinyl GABA and gamma-acetylenic GABA into neurons and astrocytes.γ-乙烯基γ-氨基丁酸和γ-乙炔基γ-氨基丁酸这两种γ-氨基丁酸转氨酶抑制剂在神经元和星形胶质细胞中的立体选择性摄取。
Neurochem Res. 1986 Nov;11(11):1497-505. doi: 10.1007/BF00965769.
9
Asymmetrical transfer of alpha-aminoisobutyric acid (AIB), leucine and lysine across the in vitro perfused human placenta.α-氨基异丁酸(AIB)、亮氨酸和赖氨酸在体外灌注人胎盘中的不对称转运。
Placenta. 1987 Mar-Apr;8(2):141-51. doi: 10.1016/0143-4004(87)90017-8.
10
Presence of gamma-aminobutyric acid and its specific receptor binding sites in the human term placenta.人足月胎盘γ-氨基丁酸及其特异性受体结合位点的存在。
Gynecol Obstet Invest. 1985;20(4):199-203. doi: 10.1159/000298994.