Document Detail

Matrix metalloproteinase-2 inhibition by temocapril and its important role in peritoneal transport.
MedLine Citation:
PMID:  23013132     Owner:  NLM     Status:  In-Data-Review    
Matrix metalloproteinase (MMP)-2 plays an important role in tissue remodelling during peritoneal injury caused by peritoneal dialysis (PD), but MMP-2 inhibitors have not yet been used clinically. Recently, it was reported that captopril, an angiotensin-converting enzyme inhibitor (ACEI), can inhibit MMP-2. To investigate the potential usefulness of ACEI during PD, the molecular interaction between the MMP-2 active site and the active form of temocapril (temocaprilat) was investigated using molecular modelling. Furthermore, the effects of temocapril on MMP-2 activity in peritoneal effluents and the peritoneal solute transport rate of PD patients were determined. Temocaprilat bound to the MMP-2 active centre and recognized two hydrophobic substrate-binding sites in the MMP-2 molecular model. Matrix metalloproteinase-2 activity in peritoneal effluents was directly inhibited by temocaprilat (IC(50) 0.47 μmol/L). In one patient given temocapril, the peritoneal solute transport rate decreased gradually during PD. Temocapril may prove to be an important candidate for development as a novel therapeutic agent for MMP-2 inhibition to prevent peritoneal injury caused by PD.
Daisuke Yamamoto; Shinji Takai; Tetsu Akimoto; Ichiro Hirahara; Chiharu Ito; Shigeaki Muto; Eiji Kusano
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Clinical and experimental pharmacology & physiology     Volume:  39     ISSN:  1440-1681     ISO Abbreviation:  Clin. Exp. Pharmacol. Physiol.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-09-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0425076     Medline TA:  Clin Exp Pharmacol Physiol     Country:  Australia    
Other Details:
Languages:  eng     Pagination:  864-8     Citation Subset:  IM    
Copyright Information:
© 2012 The Authors Clinical and Experimental Pharmacology and Physiology © 2012 Wiley Publishing Asia Pty Ltd.
Biomedical Computation Center, Osaka Medical College, Osaka, Japan.
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