Binding characteristics of SSR180575, a potent and selective peripheral benzodiazepine ligand.
The peripheral benzodiazepine receptor (PBR), has been recently shown to play a key role in the regulation of the mitochondrial process leading to apoptosis, which occurs during cardiac ischemia. The present work shows that SSR180575, a novel PBR ligand of potential interest in pathological cardiovascular indications, irreversibly and specifically binds with high affinity on both rat heart mitochondria and on a cell line transfected with the human PBR (K(d)=1.95+/-0.22 and 4.58+/-0.83nM, respectively). In conclusion, SSR180575 is a specific and potent PBR ligand which irreversible binding to PBR appears of high interest in various therapeutic indications where apoptosis occurs.
Vin
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Cardiovascular-Thrombosis Research Department, Sanofi-Synthélabo Research, Toulouse, France.
Leducq
N
N
Bono
F
F
Herbert
J M
JM
D000081:Acetamides / Q000737:chemistry* / Q000493:pharmacokinetics*; D000818:Animals; D001569:Benzodiazepines / Q000737:chemistry*; D015153:Blotting, Western; D002460:Cell Line; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000493:pharmacokinetics*; D020128:Inhibitory Concentration 50; D007511:Ischemia; D007700:Kinetics; D008024:Ligands; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014162:Transfection
D000081:Acetamides; D007211:Indoles; D008024:Ligands; C456740:SSR180575; D001569:Benzodiazepines