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J Pharmacol Exp Ther. 2000 Aug;294(2):494-9.

Functional evidence for presence of PEPT2 in rat choroid plexus: studies with glycylsarcosine.

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College of Pharmacy and Upjohn Center for Clinical Pharmacology, The University of Michigan, Ann Arbor 48109-0504, USA.


PEPT2 expression has been established in brain and, in particular, mRNA transcripts and PEPT2 protein have been identified in choroid plexus. However, there is little evidence for the functional presence of this peptide transporter in choroid plexus tissue. In this study, we examined the in vitro uptake of a model dipeptide, glycylsarcosine (GlySar), with whole tissue rat choroid plexus in artificial cerebrospinal fluid. Our findings are consistent with the known transport properties of PEPT2, including its proton dependence, lack of sodium effect, specificity, and high substrate affinity for dipeptides. Kinetic analysis showed saturable transport of GlySar with a Michaelis constant (K(m)) of 129 +/- 32 microM and a maximum velocity (V(max)) of 52.8 +/- 3.6 pmol/mg/min. GlySar uptake (1.88 microM) was not inhibited by 1.0 mM concentrations of amino acids (glycine, sarcosine, L-histidine), organic acids and bases (4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid, tetraethylammonium), or non-alpha-amino cephalosporins (cephaloridine, cephalothin). In contrast, di- and tripeptides (GlySar, glycylproline, glycylglycylhistidine), neuropeptides (carnosine), and alpha-amino cephalosporins (cefadroxil, cephalexin) inhibited the uptake of GlySar by 85 to 90% at 1.0 mM. These findings indicate that PEPT2 is functionally active in choroid plexus and that it might play a role in neuropeptide homeostasis of cerebrospinal fluid. The ability of PEPT2 to transport drugs at the choroid plexus also may be important for future drug design, delivery, and tissue-targeting considerations.

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