Metabolic stability of the LHRH antagonist antide to cell-surface peptidases.
The susceptibility to hydrolysis of LHRH and the decapeptide analogue Antide has been compared. The hydrolysis of LHRH by pig kidney brush border membranes is inhibited by phosphoramidon (I50 = 5.6 nM) implicating endopeptidase-24.11 in the initiation of hydrolysis. Under conditions in which LHRH is fully degraded by brush border membranes, Antide was completely resistant to hydrolysis. Similar results were obtained with purified preparations of both endopeptidase-24.11 and angiotensin converting enzyme. These data confirm that the remarkable duration of action of Antide is due principally to its stability to hydrolysis by cell-surface peptidases.
Medeiros
M dos S
Mdos S
Department of Biochemistry, University of Leeds, UK.
Turner
A J
AJ
Ljungqvist
A
A
Folkers
K
K
D000818:Animals; D010450:Endopeptidases / Q000378:metabolism*; D006020:Glycopeptides / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D006868:Hydrolysis; D007668:Kidney / Q000201:enzymology*; D007700:Kinetics; D008871:Microvilli / Q000201:enzymology*; D015260:Neprilysin / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism*; D013379:Substrate Specificity; D013552:Swine
D006020:Glycopeptides; D009842:Oligopeptides; D007987:Gonadotropin-Releasing Hormone; C057022:iturelix; D010450:Endopeptidases; D015260:Neprilysin; C008890:phosphoramidon