Degradation of bradykinin in semen of ram and boar.
The pattern of bradykinin (BK; Arg1-Pro2-Pro3-Gly4-Phe5-Ser6-Pro7-Phe8-Arg9)-inact iva ting peptidases in semen of boar and ram was investigated. The degradation of BK in semen was completely abolished by the metalloprotease inhibitors EDTA and o-phenanthroline. Inhibitors of angiotensin-converting enzyme (ACE; EC 3.4.15.1) and phosphoramidon, an inhibitor of neutral metalloendopeptidase (NEP; EC 3.4.24.11), were only partially effective in preventing BK degradation in semen. An additive effect was seen with simultaneous inhibition of both enzymes, resulting in complete abolition of BK degradation. HPLC analysis demonstrated that exogenous BK in semen is cleaved at Gly4-Phe5, Phe5-Ser6 and Pro7-Phe8. These results indicate that NEP and ACE are the main peptidases responsible for rapid BK inactivation in semen. The involvement of other peptidases known to be responsible for BK cleavage in other tissues and body fluids, namely carboxypeptidase N (EC 3.4.12.7), post proline cleaving enzyme (EC 3.4.21.26) and aminopeptidase P (EC 3.4.11.9) was excluded. NEP and ACE were shown to be localized mainly in seminal plasma and to a lesser extent on sperm cells.
Research Institute for Molecular Pharmacology, Berlin, Germany.
A
A
Boettger
U
U
Kertscher
C
C
Steinmann
U
U
Baeger
W E
WE
Siems
G
G
Heder
D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000378:metabolism; D000818:Animals; D001920:Bradykinin / Q000378:metabolism*; D007668:Kidney / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D001121:Lysine Carboxypeptidase / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D015260:Neprilysin / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D000085822:Prolyl Oligopeptidases; D011480:Protease Inhibitors / Q000494:pharmacology; D012661:Semen / Q000201:enzymology / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000378:metabolism; D012756:Sheep; D013552:Swine
D011480:Protease Inhibitors; D000626:Aminopeptidases; C022750:X-Pro aminopeptidase; D007703:Peptidyl-Dipeptidase A; D001121:Lysine Carboxypeptidase; D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases; D015260:Neprilysin; D001920:Bradykinin