title: Characterization of kininases in testicular cells.
abstract: 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.
authors.affiliation: Dept. of Dermatology and Andrology, Justus Liebig University, Giessen, Germany.
authors.forename: T K
authors.initials: TK
authors.lastname: Monsees
authors.forename: W
authors.initials: W
authors.lastname: Miska
authors.forename: W B
authors.initials: WB
authors.lastname: Schill
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D010450:Endopeptidases / Q000032:analysis*; D001121:Lysine Carboxypeptidase / Q000032:analysis; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012708:Sertoli Cells / Q000201:enzymology; D013737:Testis / Q000166:cytology / Q000201:enzymology*
chemical_list: D010450:Endopeptidases; D007703:Peptidyl-Dipeptidase A; D001121:Lysine Carboxypeptidase