Hemorphins inhibit angiotensin IV binding and interact with aminopeptidase N.
[125I]-Ang IV binding to rabbit collecting duct cell membranes was inhibited by hemorphins (H), a class of endogenous peptides obtained by hydrolysis of the beta chain of hemoglobin. The most potent competitors were those with a valine in their N-terminal part such as LVV-H7 and VV-H7 (IC50 = 1.3 nM) followed by VV-H8 and K6VV-H7 (5.1 nM). The same H, like Ang IV, interacted with aminopeptidase N (APN) as shown by their inhibitory effect (28-36%) on APN activity. HPLC analysis showed that only H with a N-terminal valine or leucine were hydrolyzed. Since H are detected in the body fluids, they are likely to act as endogenous competitors of Ang IV.
Garreau
I
I
Laboratoire de Génie Protéique, Pôle Sciences et Technologie, La Rochelle, France.
Chansel
D
D
Vandermeersch
S
S
Fruitier
I
I
Piot
J M
JM
Ardaillou
R
R
D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D018826:CD13 Antigens / Q000378:metabolism*; D002478:Cells, Cultured; D006454:Hemoglobins / Q000378:metabolism / Q000494:pharmacology*; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D011817:Rabbits
D006454:Hemoglobins; D010446:Peptide Fragments; D000804:Angiotensin II; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-; D018826:CD13 Antigens