jejunum, ileum, heart, liver, lung and
placenta, but not the colon, lung or spleen.
Therefore, EAAT3 is thought to be the
primary EAAT isoform responsible for
supplying anionic amino acids for general
cellular metabolic processes. EAAT1
mRNA, however, is also fairly widely
expressed outside of the brain, having been
reported in heart, lung, skeletal muscle,
placenta, and retinal Mueller and astrocyte
cells. In contrast, EAAT2 and EAAT4
expression appears limited to brain and
placenta tissues. EAAT5 has the most
restricted pattern of the EAAT family, being
expressed primarily in retinal tissue where
it is thought to play a vital role in the
retinal light response. Other expression of
EAAT5 mRNA is restricted to liver and
skeletal muscle tissue, at levels 20-fold
less than that of the retina (Arriza et al.,
1997).
Besides the brain, the one tissue that
has been shown to express EAAT1–4
mRNA is the placenta. In the placenta,
system XAG activity is thought to be
responsible for the absorption of maternal
and fetal-derived glutamate (and aspartate),
thereby providing trophoblasts with an
important source of oxidizable fuel in the
form of glutamate, generated by fetal
nitrogen assimilation from glutamine.
Therefore, to the extent that the placenta
can meet its demand for a readily oxidiz-
able fuel by glutamate, the demand for
maternal glucose for placental oxidation
may be moderated. As illustrated in Fig.
1.1, transporters capable of system XAG
activity (EAAT1–3) have been identified on
different membranes of the syncytial
trophoblast of rat placenta (Matthews et al.,
1998a). The pattern of transporter expres-
sion changes, depending on the day of
gestation. Accordingly, it is hypothesized
that the increase in EAAT1 and EAAT3
content on the apical membrane, and the
increase in EAAT3 and decrease in EAAT2
content on the basal membrane, provides
an increased capacity to absorb glutamate
(and aspartate) from the maternal and fetal
circulations during the end of gestation.
Additionally, the expression of EAAT1–3
protein by maternal decidual, giant and
spongiotrophoblast cells was also altered
with gestation. Overall, the expression of
EAAT1–3 glutamate transport proteins in
placental cells was altered in a manner12 J.C. Matthews
Fig. 1.1.Diagram illustrating the shift in transporter expression of EAAT1, EAAT2 and EAAT3 anionic amino
acid transport proteins in the labyrinth apical and basal subdomains of gestation day 14 and 20 rat
placentas. The model is based on the research of Matthews et al. (1998a) and is presented in terms of the
maternal/fetal ‘glutamine/glutamate cycle’, as described in the text.
Day 14PlacentaGlu GlnMaternal
circulationApicalBasalFetal
circulationGlu GlnGlu GlnGlu GlnLiver
EAAT2 EAAT1 EAAT3 Gln TransportDay 20