CARRIER-MEDIATED TRANSPORT OF VASOPRESSIN ACROSS THE BLOOD-BRAIN-BARRIER OF THE MOUSE
CARRIER-MEDIATED TRANSPORT OF VASOPRESSIN ACROSS THE BLOOD-BRAIN-BARRIER OF THE MOUSE
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DOI：
10.1002/jnr.490180209
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发表时间：
1987-01-01
影响因子：
4.2
通讯作者：
MICHALS, EA
中科院分区：
文献类型：
--
作者：
BANKS, WA;KASTIN, AJ;MICHALS, EA
在小鼠脑室内注射碘化 AVP 和不同量的未标记物质或候选抑制剂后，研究了脑到血液载体介导的精氨酸加压素 (AVP) 转运系统。断头后检测到的大脑残留活动被用作运输活动的主要决定因素。碘化AVP从脑中消失的半衰期为12.4分钟，Vmax为1.41nmol/g-min，表观Km为28.7nmol/g。 30 nmol 剂量的 AVP、中产素、精氨酸加压素、加压素酰胺、加压素酸、妥辛酸和赖氨酸加压素显着 (P < 0.05) 抑制转运碘化 AVP 离开大脑。 30 nmol 剂量的 AVP 对碘化物或碘酪氨酸从大脑中的转运没有影响。高效液相色谱显示，静脉注射后 2 分钟，血液中发现了 59.2% 的放射性。注射标记 AVP 在与标记 AVP 相同的位置洗脱，相比之下，静脉注射材料后在该位置洗脱的放射性为 68.8%。 2分钟。这表明完整的肽可以穿过血脑屏障，并且 AVP 的大部分降解发生在血液循环过程中。根据周围放射性的出现进行计算表明，在10分钟内，中心注射的物质的56.2％将被输送到周围。通过同时注射过量的未标记肽来抑制外周物质的出现。水负荷显着降低了 AVP 的大脑至血液转运率 40%。结论是，AVP 和一些结构相似的肽从大脑到血液的运输存在一个可饱和系统。
A brain to blood carrier-mediated transport system for arginine vasopressin (AVP) was investigated in mice after intraventricular injection of iodinated AVP and varying amounts of unlabeled material or candidate inhibitors. Residual activity in the brain detected after decapitation was used as the main determinant of transport activity. The half-time disappearance of iodinated AVP from the brain was 12.4 min, the Vmax was 1.41 nmol/g-min, and the apparent Km was 28.7 nmol/g. A 30-nmol dose of AVP, mesotocin, arginine vasotocin, pressinoic amide, pressinoic cid, tocinoic acid, and lysine vasotocin, but not oxytocin, lysine vasopressin, AVP free acid, tocinoic amide, Tyr-MIF-1, or cyclo Leu-Gly, significantly (P < 0.05) inhibited the transport of iodinated AVP out of the brain. The 30 nmol dose of AVP had no effect on the transport of iodide or iodotyrosine out of the brain. High-performance liquid chromatography showed that 59.2% of the radioactivity found in the blood 2 min after an i.c.v. injection of labeled AVP eluted at the same position as labeled AVP compared with 68.8% of radioactivity eluting at that position after material was infused i.v. for 2 min. This indicates that intact peptide is transported across the blood-brain barrier and that most of the degradation of AVP occurs during circulation in the blood. Calculations based on the appearance of radioactivity in the periphery showed that 56.2% of the material injected centrally would have been transported into the periphery by 10 min. This appearance of material in the periphery was inhibited by the simultaneous injection of an excess of unlabeled peptide. Water loading significantly decreased the brain to blood transport rate of AVP by 40%. It is concluded that a saturable system exists for brain to blood transport of AVP and some structurally similar peptides.