Renin inhibitor: transport mechanism in rat small intestinal brush-border membrane vesicles.
The transport characteristics of the renin inhibitor ((3S,4S)-4-[N-morpholinoacetyl-(1-naphthyl)-L-alanyl-N-methyl-(4-t hiazolyl)-L- alanyl]amino-3-hydroxy-5-cyclohexyl-1-(4-pyridyl)-1-pentanone; CH3-18) in rat small intestinal brush-border membrane vesicles (BBMV) were examined by a rapid filtration technique. The uptake of CH3-18 was markedly stimulated by an inwardly directed H+ gradient (pH 7.5 inside, pH 5.5 outside) and showed an uphill transport. It was competitively inhibited by tripeptides and tetrapeptides, but not by amino acids or dipeptides. A countertransport effect on the uptake of CH3-18 was observed in the vesicle preloaded with a tripeptide. Effects of the fragments of several renin inhibitors were evaluated by their inhibitory and countertransport effects on the uptake of CH3-18. The morpholino group at the N-terminal was found to be important for the uptake of CH3-18.
Hashimoto
N
N
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Fujioka
T
T
Toyoda
T
T
Muranushi
N
N
Hirano
K
K
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001693:Biological Transport, Active; D004151:Dipeptides / Q000493:pharmacokinetics*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology*; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism*; D007769:Lactams; D008297:Male; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D008969:Molecular Sequence Data; D009025:Morpholines / Q000493:pharmacokinetics*; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D000092502:Renin Inhibitors
D000596:Amino Acids; D000900:Anti-Bacterial Agents; D004151:Dipeptides; D007769:Lactams; D009025:Morpholines; D009842:Oligopeptides; D010446:Peptide Fragments; D000092502:Renin Inhibitors; C091961:4-N-(morpholinoacetyl-(1-naphthyl)-alanyl-N-methyl-(4-thiazolyl)-alanyl)amino-3-hydroxy-5-cyclohexyl-1-(4-pyridyl)-1-pentanone