Springer Online Journal Archives 1860-2000
Chemistry and Pharmacology
Abstract Purpose. To examine the mechanism of inhibition of glycylsarcosine(GlySar) transport by quinapril and enalapril, and whether or notangiotensin converting enzyme (ACE) inhibitors are transported by PEPT2as well as by PEPT1. Methods. Xenopus laevis oocytes were cRNA-injected with rat PEPT1or PEPT2 and the transport kinetics of radiolabeled GlySar were studiedin the absence and presence of quinapril and enalapril. Thetwo-microelectrode voltage-clamp technique was also performed to probe theelectrogenic uptake of captopril, quinapril and enalapril. Results. Kinetic analyses demonstrated that quinapril inhibited theuptake of GlySar in a noncompetitive manner in Xenopus oocytesinjected with PEPT1 or PEPT2 (Ki = 0.8 or 0.4 mM, respectively).In contrast, a competitive interaction was observed between GlySarand enalapril (Ki = 10.8 mM for PEPT1 or 4.3 mM for PEPT2).Most significantly, captopril and enalapril, but not quinapril, inducedinwardly-directed currents in both PEPT1- and PEPT2-expressedoocytes. Conclusions. These results are unique in providing direct evidence forthe substrate recognition and transport of some ACE inhibitors by thehigh- and low-affinity oligopeptide transporters. Our findings point todifferences between PEPT1 and PEPT2 in their affinity to, rather thanin their specificity for, ACE inhibitors.
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