Abstract
The transport characteristics of the renin inhibitor ((3S,4S)-4-[N-morpholinoacetyl-(l-naphthyl)-L-alanyl-N-methyl-(4-thiazolyl)-L-alanyl]amino-3-hydroxy-5-cyclohexyl-l-(4-pyridyl)-l-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.
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Hashimoto, N., Fujioka, T., Toyoda, T. et al. Renin Inhibitor: Transport Mechanism in Rat Small Intestinal Brush-Border Membrane Vesicles. Pharm Res 11, 1448–1451 (1994). https://doi.org/10.1023/A:1018900124257
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DOI: https://doi.org/10.1023/A:1018900124257