Effects of kinins on mammalian spermatozoa and the impact of peptidolytic enzymes.
Effects of kinins, mainly bradykinin (Bk), and other components of the kallikrein-kinin system on sperm motility and further fertility-related functions have been described repeatedly. However, reported data are in part controversial and the mechanism of kinin effects on sperm motility is not yet understood. In the present report we describe a significant promoting effect of Bk on sperm motility at subnanomolar concentrations. This effect was stabilized and even increased by suppression of Bk hydrolysis in semen samples. As sperm membrane-bound angiotensin-converting enzyme and neutral metalloendopeptidase are mainly involved in Bk hydrolysis, an effective cocktail of enzyme inhibitors promoting the sperm motility consists of phosphoramidon and lisinopril (both at 10-7 m). The effects of Bk on sperm cells are not mediated by the B2 Bk receptor. Using several biochemical, molecular and genetic methods we could not detect any Bk receptor on spermatozoa.
Siems
W-E
WE
Institute of Molecular Pharmacology, Berlin, Germany. Siems@fmp-berlin.de
Maul
B
B
Wiesner
B
B
Becker
M
M
Walther
T
T
Rothe
L
L
Winkler
A
A
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000378:metabolism / Q000494:pharmacology*; D002118:Calcium / Q000032:analysis; D002417:Cattle; D006020:Glycopeptides / Q000494:pharmacology; D006801:Humans; D006868:Hydrolysis; D017706:Lisinopril / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D015260:Neprilysin / Q000037:antagonists & inhibitors / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger; D051381:Rats; D017208:Rats, Wistar; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D013081:Sperm Motility / Q000187:drug effects*; D013094:Spermatozoa / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D006020:Glycopeptides; D011480:Protease Inhibitors; D012333:RNA, Messenger; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D017706:Lisinopril; D010447:Peptide Hydrolases; D007703:Peptidyl-Dipeptidase A; D015260:Neprilysin; D001920:Bradykinin; D002118:Calcium; C008890:phosphoramidon