Angiotensin 1-9 and 1-7 Release in Human HeartRole of Cathepsin A
作者:
Herbert Jackman,
Malek Massad,
Marin Sekosan,
Fulong Tan,
Viktor Brovkovych,
Branislav Marcic,
Ervin Erdös,
期刊:
Hypertension: Journal of The American Heart Association
(OVID Available online 2002)
卷期:
Volume 39,
issue 5
页码: 976-981
ISSN:0194-911X
年代: 2002
出版商: OVID
关键词: peptides;angiotensin-converting enzyme;receptors, bradykinin;nitric oxide
数据来源: OVID
摘要:
Human heart tissue enzymes cleave angiotensin (Ang) I to release Ang 1-9, Ang II, or Ang 1-7. In atrial homogenate preparations, cathepsin A (deamidase) is responsible for 65% of the liberated Ang 1-9. Ang 1-7 was released (88% to 100%) by a metallopeptidase, as established with peptidase inhibitors. Ang II was liberated to about equal degrees by ACE and chymase-type enzymes. Cathepsin A’s presence in heart tissue was also proven because it deamidated enkephalinamide substrate by immunoprecipitation of cathepsin A with antiserum to human recombinant enzyme and by immunohistochemistry. In immunohistochemistry, cathepsin A was detected in myocytes of atrial tissue. The products of Ang I cleavage, Ang 1-9 and Ang 1-7, potentiated the effect of an ACE-resistant bradykinin analog and enhanced kinin effect on the B2receptor in Chinese hamster ovary cells transfected to express human ACE and B2(CHO/AB), and in human pulmonary arterial endothelial cells. Ang 1-9 and 1-7 augmented arachidonic acid and nitric oxide (NO) release by kinin. Direct assay of NO liberation by bradykinin from endothelial cells was potentiated at 10 nmol/L concentration, 2.4-fold (Ang 1-9) and 2.1-fold (Ang 1-7); in higher concentrations, Ang 1-9 was significantly more active than Ang 1-7. Both peptides had traces of activity in the absence of bradykinin. Ang 1-9 and Ang 1-7 potentiated bradykinin action on the B2receptor by raising arachidonic acid and NO release at much lower concentrations than their 50% inhibition concentrations (IC50s) with ACE. They probably induce conformational changes in the ACE/B2receptor complex via interaction with ACE.
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