RT Journal Article
SR Electronic
T1 Functional Evidence for Presence of PEPT2 in Rat Choroid Plexus: Studies with Glycylsarcosine
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 494
OP 499
VO 294
IS 2
A1 Nathan S. Teuscher
A1 Alexander Novotny
A1 Richard F. Keep
A1 David E. Smith
YR 2000
UL http://jpet.aspetjournals.org/content/294/2/494.abstract
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