PT  - JOURNAL ARTICLE
AU  - Nathan S. Teuscher
AU  - Alexander Novotny
AU  - Richard F. Keep
AU  - David E. Smith
TI  - Functional Evidence for Presence of PEPT2 in Rat Choroid Plexus: Studies with Glycylsarcosine
DP  - 2000 Aug 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 494--499
VI  - 294
IP  - 2
4099  - http://jpet.aspetjournals.org/content/294/2/494.short
4100  - http://jpet.aspetjournals.org/content/294/2/494.full
SO  - J Pharmacol Exp Ther2000 Aug 01; 294
AB  - 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 (Km) of 129 ± 32 μM and a maximum velocity (Vmax) of 52.8 ± 3.6 pmol/mg/min. GlySar uptake (1.88 μM) 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-α-amino cephalosporins (cephaloridine, cephalothin). In contrast, di- and tripeptides (GlySar, glycylproline, glycylglycylhistidine), neuropeptides (carnosine), and α-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. The American Society for Pharmacology and Experimental Therapeutics