Comparative effects of angiotensin IV and two hemorphins on angiotensin-converting enzyme activity.
The role of angiotensin IV (AngIV) in the regulation of angiotensin-converting enzyme (ACE) was studied in vitro. This study demonstrates that this active fragment appeared as a novel endogenous ACE inhibitor. Inhibitory kinetic studies revealed that AngIV acts as a purely competitive inhibitor with a K(i) value of 35 microM. AngIV was found to be quite resistant to ACE hydrolysis opposite to hemorphins which are both ACE inhibitors and substrates. In order to confirm a putative role of AngIV and hemorphins in the Renin-Angiotensin system (RAS) regulation, we studied their influence on AngI conversion. We noticed that 16.7 microM of both peptides decreased more than 50% of AngI conversion to AngII in vitro. The capacity of hemorphins, particularly LVVH-7, and AngIV to inhibit ACE activity here suggests a synergistic relation between these two peptides and the regulation of RAS.
Laboratoire de Génie Protéique et Cellulaire, EA 3169, Pôle Sciences et Technologie, Bâtiment Marie Curie, Avenue Michel Crépeau, Université de La Rochelle, UFR Sciences, 17042 La Rochelle Cedex 1, France. ifruitie@univ-Ir.fr
Ingrid
I
Fruitier-Arnaudin
Marie
M
Cohen
Stéphanie
S
Bordenave
Frédéric
F
Sannier
Jean-Marie
JM
Piot
D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D006454:Hemoglobins / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D007703:Peptidyl-Dipeptidase A / Q000187:drug effects* / Q000378:metabolism; D051381:Rats
D006454:Hemoglobins; D010446:Peptide Fragments; D000804:Angiotensin II; C085122:hemorphin 7; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-; C074309:LVV-hemorphin-7; C094394:VV-hemorphin-7; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A