Monsees T K, Miska W, Schill W B
Dept. of Dermatology and Andrology, Justus Liebig University, Giessen, Germany.
Immunopharmacology. 1996 May;32(1-3):169-71. doi: 10.1016/0162-3109(95)00084-4.
Kininases are an important part of the kallikrein-kinin system. We investigated the pattern of kininases in rat Sertoli cells. Sertoli cells are found in the seminifereous tubule of the testis and play a key role in spermatogenesis. Bradykinin was actively cleaved by cultivated Sertoli cells at the Pro7-Phe8, Phe5-Ser6 and Gly4-Phe5 bonds as demonstrated by high performance liquid chromatography analysis. Addition of phosphoramidon and thiorphan, which are specific inhibitors of neutral metalloendopeptidase 3.4.24.11 (NEP), strongly inhibited the degradation of bradykinin. In contrast, the kininase type II-specific inhibitors captopril and enalapril were only partially effective in preventing peptidolysis. NEP and kininase type II were shown to be located in Sertoli cell membranes. The action of kininase type I leads to the formation of the metabolite bradykinin (1-8) which could be detected in small amounts by HPLC analysis. Cleavage of the Ph5-Ser6 bond might be caused by the action of the endopeptidases 24.15 and 24.16, which are phosphoramidon-insensitive. Our results indicate that neutral metalloendopeptidase 24.11 is the main kininase responsible for rapid bradykinin inactivation in Sertoli cells. Further kininases with minor activities are the kininases type I and II and probably the metalloendopeptidases 24.15 and 24.16.
激肽酶是激肽释放酶 - 激肽系统的重要组成部分。我们研究了大鼠支持细胞中激肽酶的模式。支持细胞存在于睾丸的生精小管中，在精子发生过程中起关键作用。高效液相色谱分析表明，培养的支持细胞能在Pro7 - Phe8、Phe5 - Ser6和Gly4 - Phe5键处积极裂解缓激肽。添加磷酰胺脒和噻吗洛尔，这两种中性金属内肽酶3.4.24.11（NEP）的特异性抑制剂，能强烈抑制缓激肽的降解。相比之下，激肽酶II型特异性抑制剂卡托普利和依那普利在防止肽分解方面仅部分有效。NEP和激肽酶II型定位于支持细胞膜上。激肽酶I型的作用导致代谢产物缓激肽（1 - 8）的形成，通过高效液相色谱分析可检测到少量该产物。Ph5 - Ser6键的裂解可能是由对磷酰胺脒不敏感的内肽酶24.15和24.16的作用引起的。我们的结果表明，中性金属内肽酶24.11是支持细胞中负责快速使缓激肽失活的主要激肽酶。活性较小的其他激肽酶是激肽酶I型和II型，可能还有金属内肽酶24.15和24.16。
