Augustijns P F, Ng K Y, Williams T M, Borchardt R T
Department of Pharmaceutical Chemistry, University of Kansas, Lawrence 66045, USA.
Biochem Biophys Res Commun. 1995 May 25;210(3):987-94. doi: 10.1006/bbrc.1995.1754.
Previous studies have shown that the metabolism of delta sleep-inducing peptide (DSIP) in the blood-brain barrier (BBB) is catalyzed by amino-peptidases. In this study, we have shown that peptidyl dipeptidase A in cultured bovine brain microvessel endothelial cells (BBMEC), a model of the BBB, and a purified form of this enzyme can also metabolize DSIP by sequential hydrolyses of dipeptides or tripeptides from the carboxyl terminus of this nonapeptide. Both the dipeptidase and tripeptidase activity associated with peptidyl dipeptidase A can be inhibited by captopril. Total stabilization of DSIP to metabolism in BBMEC could be achieved by inclusion of an inhibitor of peptidyl dipeptidase A (e.g., captopril) and an inhibitor of aminopeptidases (e.g., bestatin).
先前的研究表明，血脑屏障（BBB）中诱导δ波睡眠肽（DSIP）的代谢是由氨肽酶催化的。在本研究中，我们发现，作为血脑屏障模型的培养牛脑微血管内皮细胞（BBMEC）中的肽基二肽酶A以及该酶的纯化形式，也能够通过从这种九肽的羧基末端依次水解二肽或三肽来代谢DSIP。与肽基二肽酶A相关的二肽酶和三肽酶活性均可被卡托普利抑制。通过加入肽基二肽酶A的抑制剂（如卡托普利）和氨肽酶的抑制剂（如贝司他汀），可以实现DSIP在BBMEC中代谢的完全稳定。
