Pharmaceutical Research

, Volume 17, Issue 5, pp 526–532

Differential Recognition of ACE Inhibitors in Xenopus Laevis Oocytes Expressing Rat PEPT1 and PEPT2

  • Tong Zhu
  • Xing-Zhen Chen
  • Angela Steel
  • Matthias A. Hediger
  • David E. Smith
Article
  • 161 Downloads

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.

ACE inhibitors PEPT1 PEPT2 captopril enalapril quinapril 

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Copyright information

© Plenum Publishing Corporation 2000

Authors and Affiliations

  • Tong Zhu
    • 1
  • Xing-Zhen Chen
    • 2
  • Angela Steel
    • 2
  • Matthias A. Hediger
    • 2
  • David E. Smith
    • 4
  1. 1.College of Pharmacy and Upjohn Center for Clinical PharmacologyThe University of MichiganAnn Arbor
  2. 2.Membrane Biology Program and Renal DivisionBrigham and Women's Hospital, Harvard Medical SchoolBoston
  3. 3.Anti-Infectives ResearchSmithKline Beecham PharmaceuticalsCollegeville
  4. 4.College of Pharmacy and Upjohn Center for Clinical PharmacologyThe University of MichiganAnn Arbor

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