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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
|
| pubmed:dateCreated |
1997-3-24
|
| pubmed:abstractText |
Angiotensin-converting enzyme (ACE) has two enzymatically active domains: a C-domain in the carboxy terminal region and an N-domain in the amino terminal region. We based the pharmacologic characterization of these sites on the rat testis-lung model. In testis, only a truncate form of ACE is present (C-site), whereas both N- and C-sites are present in lung. In this model, captopril was shown to be N-selective and delaprilat to be C-selective. Ro 31-8472, a cilazapril derivative, and enalaprilat proved to be not site selective. We used these drugs to evaluate the affinity of C and N sites in various human tissues involved in the cardiovascular actions of ACE and used [125I]Ro31-8472 as ligand. The number and affinity of ACE binding sites were 17,680 +/- 2,345 fmol/mg protein (Kd = 0.32 +/- 0.04 nM) in lung, 560 +/- 65 (Kd = 0.36 +/- 0.05 nM) in heart, 237 +/- 51 (Kd = 0.37 +/- 0.06 nM) in coronary artery, 236 +/- 63 (Kd = 0.14 +/- 0.05 nM) in saphenous vein, and 603 +/- 121 (Kd = 0.50 +/- 0.06 nM) in mammary artery. The affinity (pKi) of captopril for the N sites ranged from 9.40 +/- 0.14 (lung) to 8.41 +/- 0.10 (coronary artery). The affinity for the C-site by delaprilat ranged from 9.97 +/- 0.15 (coronary artery) to 9.10 +/- 0.14 (mammary artery). Therefore, the affinity of C- and N-sites of ACE for ACE inhibitor (ACEI) drugs is different according to the organ involved. Because ACE is a glycosylated enzyme and glycosylation is organ dependent, we suggest that organ-specific glycosylation affects the binding characteristics of ACE inhibitors to N- or C-site of human tissular ACE.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Angiotensin-Converting Enzyme...,
http://linkedlifedata.com/resource/pubmed/chemical/Captopril,
http://linkedlifedata.com/resource/pubmed/chemical/Enalaprilat,
http://linkedlifedata.com/resource/pubmed/chemical/Iodine Radioisotopes,
http://linkedlifedata.com/resource/pubmed/chemical/Peptidyl-Dipeptidase A,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridazines,
http://linkedlifedata.com/resource/pubmed/chemical/Ro 31-8472
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Oct
|
| pubmed:issn |
0160-2446
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
28
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
494-9
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:8891872-Adult,
pubmed-meshheading:8891872-Angiotensin-Converting Enzyme Inhibitors,
pubmed-meshheading:8891872-Animals,
pubmed-meshheading:8891872-Arteries,
pubmed-meshheading:8891872-Binding Sites,
pubmed-meshheading:8891872-Captopril,
pubmed-meshheading:8891872-Cell Membrane,
pubmed-meshheading:8891872-Coronary Vessels,
pubmed-meshheading:8891872-Enalaprilat,
pubmed-meshheading:8891872-Female,
pubmed-meshheading:8891872-Humans,
pubmed-meshheading:8891872-Iodine Radioisotopes,
pubmed-meshheading:8891872-Lung,
pubmed-meshheading:8891872-Male,
pubmed-meshheading:8891872-Mammary Arteries,
pubmed-meshheading:8891872-Myocardium,
pubmed-meshheading:8891872-Peptidyl-Dipeptidase A,
pubmed-meshheading:8891872-Pyridazines,
pubmed-meshheading:8891872-Radioligand Assay,
pubmed-meshheading:8891872-Rats,
pubmed-meshheading:8891872-Saphenous Vein,
pubmed-meshheading:8891872-Testis,
pubmed-meshheading:8891872-Veins
|
| pubmed:year |
1996
|
| pubmed:articleTitle |
Affinity of angiotensin I-converting enzyme (ACE) inhibitors for N- and C-binding sites of human ACE is different in heart, lung, arteries, and veins.
|
| pubmed:affiliation |
Endocrinology Department, L Sacco Hospital (Vialba), Milan, Italy.
|
| pubmed:publicationType |
Journal Article,
In Vitro
|