, Volume 22, Issue 8, pp 1281-1286
Date: 03 Aug 2005

Glycyl-l-Glutamine Disposition in Rat Choroid Plexus Epithelial Cells in Primary Culture: Role of PEPT2

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The purpose of this research was to determine the polarity and directionality of the PEPT2-mediated uptake and transepithelial transport of the neuropeptide glycyl-l-glutamine (GlyGln) in choroid plexus.


The transport kinetics of [3H]GlyGln was studied in neonatal rat choroid plexus epithelial cells in primary culture grown on laminin-coated Transwell filter inserts. Using a bicarbonate artificial cerebrospinal fluid (CSF) buffer (pH 7.4) at 37°C, GlyGln studies were performed as a function of time, substrate concentration, and the presence of potential inhibitors (at 1 mM).


GlyGln (2 μM) accumulation was about three to four times greater when introduced from the apical (CSF-facing) as opposed to the basal (blood-facing) side of the cell monolayer, and transepithelial transport was about two times greater in the apical-to-basal direction. The apical uptake of radiolabeled GlyGln (2 μM) was inhibited significantly by dipeptides (i.e., unlabeled GlyGln and cysteinylglycine) and some neuropeptides (i.e., carnosine, N-acetylaspartylglutamate, kyotorphin), but was unaffected by amino acids (i.e., glycine, glutamine) as well as by [d-Arg2]-kyotorphin and glutathione. The concentration-dependent apical uptake of GlyGln (2–1000 μM) was characterized by a high-affinity process (i.e., Vmax of 72 pmol/mg/min; Km of 136 μM), consistent with the properties of PEPT2. The intracellular hydrolysis of GlyGln was extensive, however, with only 40% of the dipeptide remaining intact after 1 h.


The results demonstrate that PEPT2 plays an important role in regulating the apical uptake of GlyGln at the blood–CSF interface. Once inside the cell, GlyGln is rapidly degraded to its constitutive amino acids for further processing.