Pharmaceutical Research

, Volume 18, Issue 6, pp 807–813

PEPT2-Mediated Uptake of Neuropeptides in Rat Choroid Plexus

  • Nathan S. Teuscher
  • Richard F. Keep
  • David E. Smith

DOI: 10.1023/A:1011088413043

Cite this article as:
Teuscher, N.S., Keep, R.F. & Smith, D.E. Pharm Res (2001) 18: 807. doi:10.1023/A:1011088413043


Purpose. The peptide transporter PEPT2 was recently shown to be functionally active in rat choroid plexus, suggesting that it may play a role in neuropeptide homeostasis in the cerebrospinal fluid. This study, therefore, examined the role of PEPT2 in mediating neuropeptide uptake into choroid plexus.

Methods. Whole-tissue rat choroid plexus uptake studies were performed on GlySar in the absence and presence of neuropeptides and on carnosine.

Results. The neuropeptides NAAG, CysGly, GlyGln, kyotorphin, and carnosine inhibited the uptake of radiolabeled GlySar at 1.0 mM concentrations. In contrast, TRH, [D-Arg2]-kyotorphin, glutathione, and homocarnosine did not inhibit GlySar uptake. Kyotorphin, an analgesic, was a competitive inhibitor of GlySar with a Ki of 8.0 μM. The direct uptake of carnosine was also shown to be mediated by PEPT2 in isolated choroid plexus (Km = 39.3 μM; Vmax = 73.9 pmol/mg/min). Radiolabeled carnosine uptake was inhibited by 1.0 mM concentrations of GlySar or carnosine but not homocarnosine, L-histidine, or β-alanine.

Conclusions. These findings indicate that PEPT2 mediates the uptake of a diverse group of neuropeptides in choroid plexus, and suggests a role for PEPT2 in the regulation of neuropeptides, peptide fragments, and peptidomimetics in cerebrospinal fluid.

PEPT2GlySarcarnosineneuropeptideschoroid plexus

Copyright information

© Plenum Publishing Corporation 2001

Authors and Affiliations

  • Nathan S. Teuscher
    • 1
  • Richard F. Keep
    • 2
  • David E. Smith
    • 1
  1. 1.College of Pharmacy and Upjohn Center for Clinical PharmacologyThe University of MichiganAnn Arbor
  2. 2.Department of Surgery (Neurosurgery) and PhysiologyThe University of MichiganAnn Arbor