An inhibitor of endopeptidase-24.15 blocks the degradation of intraventricularly administered dynorphins.
An inhibitor of endopeptidase-24.15 blocks the degradation of intraventricularly administered dynorphins.
复制标题
肽链内切酶 24.15 抑制剂可阻止脑室内注射强啡肽的降解。
DOI：
10.1111/j.1471-4159.1990.tb04177.x
复制
发表时间：
1990
影响因子：
4.7
通讯作者：
Ayala,JM
中科院分区：
文献类型：
--
作者：
Molineaux,CJ;Ayala,JM
采用脑室-脑池灌注技术研究了八肽dynorphin (Dyn) A‐（1-8）在体内被内肽酶EC 3.4.24.15 （EP‐24,15）转化为Leu5‐enkephalin （LE）的情况。在EP - 24.15抑制剂orn - [1 - (R，S) -羧基- 3 -苯丙基]- Ala - Ala - Phe -对氨基苯甲酸酯（cFPAAF - pAB）存在或不存在的情况下，通过放置在氨基甲酸乙酯麻醉大鼠侧脑室的导管给药多肽。用放射免疫法检测从大池中取出的脑脊液样本中Dyn - like肽和LE的浓度。在缺乏抑制剂的情况下，给药的Dyn A‐（1-8）在脑脊液中回收率<5%。通常在脑脊液中没有发现的免疫反应性LE在Dyn A‐（1-8）输注后含量迅速增加，这一观察结果表明较大的肽转化为LE。当抑制剂cFPAAF - pAB与Dyn A‐（1-8）共给药时，5min后免疫反应性Dyn A‐（1-8）的浓度比无抑制剂时高40倍。血管紧张素转换酶抑制剂卡托普利降低Dyn A‐（1-8）的降解程度要小得多。EP‐24.15抑制剂也对其他Dyn‐样肽具有一定的保护作用。在大鼠脑脊液中未发现EP - 24.15活性，而在脉络膜丛中发现了高活性。综上所述，这些数据清楚地表明EP - 24.15的一种外酶形式能迅速将脑室内给药的Dyn样肽转化为LE。关键词：脑啡肽-脑啡肽-脑啡酶-外泌酶-脑室池-血管紧张素转换酶[0]张建军，张建军，张建军，等。内肽酶- 24.15抑制剂抑制脑内给药促啡肽降解的研究进展。神经化学，55,611-618（1990）。
Conversion of the octapeptide dynorphin (Dyn) A‐(1–8) to Leu5‐enkephalin (LE) by endopeptidase EC 3.4.24.15 (EP‐24,15) in vivo was examined using the technique of ventriculocisternal perfusion. Peptides were administered intra‐cerebroventricularly in the presence or absence of the EP‐24.15 inhibitorN‐[1‐(R,S)‐carboxy‐3‐phenylpropyl]‐Ala‐Ala‐Phe‐p‐aminobenzoate (cFPAAF‐pAB) via cannulae placed into the lateral ventricle of urethane‐anesthetized rats. The concentration of Dyn‐like peptides and LE within the CSF was monitored by radioimmunoassay in samples of CSF taken from a second cannula placed in the cisterna magna. In the absence of inhibitor, <5% of the Dyn A‐(1–8) administered was recovered in CSF. Immunoreactive LE, which is normally not found in CSF, increased rapidly in content following Dyn A‐(1–8) infusion, an observation suggesting that the larger peptide is converted to LE. When the inhibitor cFPAAF‐pAB was coadministered with Dyn A‐(1–8), the concentration of immunoreactive Dyn A‐(1–8) after 5 min was 40 times higher than that found in the absence of inhibitor. The angiotensin converting enzyme inhibitor captopril reduced the degradation of Dyn A‐(1–8) to a much lesser degree. The inhibitor of EP‐24.15 also afforded some protection of other Dyn‐like peptides. No EP‐24.15 activity was found in rat CSF, whereas high activity was found in the choroid plexus. Taken together, these data clearly indicate that an ectoenzyme form of EP‐24.15 rapidly converts intra‐cerebroventricularly administered Dyn‐like peptides to LE. Key Words: Dynorphin—Enkephalin—Enkephalinase—Ectoenzyme—Ventriculocisternal—Angiotensin converting enzyme.Molíneaux C. J. and Ayala J. M. An inhibitor of endopeptidase‐24.15 blocks the degradation of intraventricularly administered dynorphins.J. Neurochem. 55, 611–618 (1990).