Loading...
Please wait, while we are loading the content...
Similar Documents
Substrate dependence of angiotensin I-converting enzyme inhibition: captopril displays a partial selectivity for inhibition of N-acetyl-seryl-aspartyl-lysyl-proline hydrolysis compared with that of angiotensin I.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Michaud, Audrey Williams, Tracy Ann Corvol, Pierre |
| Copyright Year | 1997 |
| Abstract | Angiotensin I-converting enzyme (ACE) is composed of two highly similar domains (referred to here as the N and C domains) that play a central role in blood pressure regulation; ACE inhibitors are widely used in the treatment of hypertension. However, the negative regulator of hematopoiesis, N-acetyl-seryl-aspartyl-lysyl-prolyl (AcSDKP), is a specific substrate of the N domain-active site; thus, in addition to the cardiovascular function of ACE, the enzyme may be involved in hematopoietic stem cell regulation, raising the interest of designing N domain-specific ACE inhibitors. We analyzed the inhibition of angiotensin I and AcSDKP hydrolysis as well as that of three synthetic ACE substrates by wild-type ACE and the N and C domains by using a range of specific ACE inhibitors. We demonstrate that captopril, lisinopril, and fosinoprilat are potent inhibitors of AcSDKP hydrolysis by wild-type ACE, with K(i) values in the subnanomolar range. However, of the inhibitors tested, captopril is the only compound able to differentiate to some degree between AcSDKP and angiotensin I inhibition of hydrolysis by wild-type ACE: the K(i) value with AcSDKP as substrate was 16-fold lower than that with angiotensin I as substrate. This raises the possibility of using captopril to enhance plasma AcSDKP levels with the aim of normal hematopoeitic stem cell protection during chemotherapy and a limited effect on the cardiovascular function of ACE. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://molpharm.aspetjournals.org/content/molpharm/51/6/1070.full.pdf |
| PubMed reference number | 9187274v1 |
| Volume Number | 51 |
| Issue Number | 6 |
| Journal | Molecular pharmacology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Angiotensin I Angiotensin-Converting Enzyme Inhibitors Angiotensins Captopril Cardiovascular Diseases Cytoprotection Dependence Hematopoiesis Hematopoietic stem cells Hypertensive disease Lisinopril Procollagen-Proline Dioxygenase Proline fosinoprilat goralatide |
| Content Type | Text |
| Resource Type | Article |
