The signaling action of neuropeptides in the is terminated by breakdown thr
ough extracellular peptidases and subsequent removal of the peptide fragmen
ts from the extracellular fluid via specific transporter proteins. Here we
describe the anatomical distribution in the rat nervous system of the recen
tly isolated high affinity peptide transporter PEPT2. Using nonisotopic in
situ hybridization we demonstrate that PEPT2 mRNA is expressed in brain by
astrocyte, subependymal cells, ependymal cells and epithelial cells of chor
oid plexus. Furthermore, PEPT2 is expressed in retina by Muller cells and i
n dorsal root ganglia by satellite cells. The mRNA levels of PEPT2 in astro
cytes are moderate and relatively homogenous throughout the brain except fo
r an area in ventral forebrain where PEPT2 levels are below average. PEPT2
mRNA expression is weakly upregulated in reactive astrocytes that were stim
ulated through an injection of the glutamatergic neurotoxin quinolinic acid
. These data suggest that removal of neuropeptide fragments from brain extr
acellular fluid occurs via PEPT2 expressed in astrocytes, ependymal cells a
nd choroid plexus epithelial cells.