PERMEABILITY OF THE BLOOD-BRAIN-BARRIER TO THE NEUROTENSIN(8-13) ANALOG NT1

被引：27

作者：

BANKS, WA ^{[1
]}

WUSTROW, DJ ^{[1
]}

CODY, WL ^{[1
]}

DAVIS, MD ^{[1
]}

KASTIN, AJ ^{[1
]}

机构：

[1] WARNER LAMBERT PARKE DAVIS, PARKE DAVIS PHARMACEUT RES DIV, ANN ARBOR, MI USA

来源：

BRAIN RESEARCH | 1995年 / 695卷 / 01期

关键词：

BEHAVIOR; SATURABLE TRANSPORT; THERAPEUTICS; PHARMACOKINETICS; MOUSE;

D O I：

10.1016/0006-8993(95)00836-F

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Neurotensin (NT) has been suggested to be a neuropeptide with therapeutic potential. We used multiple-time regression analysis to measure the unidirectional influx constant (K-i) of a tritiated analog of NT8-13, NT1, with improved metabolic stability. The K-i of [H-3]NT1 across the blood-brain barrier (BBB) was 5.12(10(-4)) ml/g-min and was decreased 66% by unlabeled NT1 system. The amount of NT1 crossing the BBB, 0.087% of the injected dose per gram of brain, is consistent with its exerting central effects after peripheral administration. The stable [H-3]NT1 crossed the BBB in intact form as assessed by HPLC and completely crossed the endothelial cells that comprise the BBB as assessed by the capillary depletion method. The presence of a transport system could be important for the development of NT analogs.

引用

页码：59 / 63

页数：5

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