Human placental syncytiotrophoblast expresses two pharmacologically distinguishable types of Na+-H+ exchangers, NHE-1 in the maternal-facing (brush border) membrane and NHE-2 in the fetal-facing (basal) membrane

Abstract

We investigated whether highly purified preparations of basal (fetal-facing) membrane isolated from normal term human placentas possess Na(+)-H+ exchanger activity. Uptake of Na+ into basal membrane vesicles was stimulated many-fold by an outwardly directed H+ gradient. This H(+)-gradient-dependent uptake was inhibitable by amiloride and its analogues. Na+ uptake in these vesicles did not occur via a Na+ channel, as it was not influenced by changes in membrane potential and, in addition, was inhibited by benzamil only at high micromolar concentrations. The results indicate that the human placental basal membrane possesses Na(+)-H+ exchanger activity. We then studied whether this exchanger is similar to or distinct from the Na(+)-H+ exchanger described in brush border (maternal-facing) membrane preparations. For this purpose, we compared the pharmacological characteristics of the basal membrane Na(+)-H+ exchanger with those of the brush border membrane Na(+)-H+ exchanger. The basal membrane exchanger was about 20-fold less sensitive to inhibition by amiloride and about 70-fold less sensitive to inhibition by dimethylamiloride than was the brush border membrane exchanger. The exchanger activity in both membrane preparations was inhibitable by clonidine and cimetidine, but the inhibition patterns with these compounds were markedly different between basal and brush border membrane preparations. These data demonstrate that the basal membrane Na(+)-H+ exchanger is distinct from the brush border membrane Na(+)-H+ exchanger. The pharmacological profiles of these exchangers indicate that the human placental brush border membrane possesses the housekeeping or non-epithelial type Na(+)-H+ exchanger (NHE-1), whereas the basal membrane possesses the epithelial or apical type Na(+)-H+ exchanger (NHE-2).

Placental transporter activity and expression in relation to fetal growth

“…The Na+-H+ exchanger is present in both microvillous and basal plasma membranes of the syncytiotrophoblast (Kulanthaivel, Furesz, Moe, Smith, Mahesh, Leibach & Ganapathy, 1992; Fig. 1).…”

Altered activity of the system A amino acid transporter in microvillous membrane vesicles from placentas of macrosomic babies born to diabetic women.

“…The NHE-1 isoform is postulated to be associated with "housekeeping" functions such as cellular pH regulation (13). The second aim of this study was therefore to determine whether there were any changes in MVM Na+/H+ exchanger activity in diabetic pregnancies associated with FM, a clinical situation where the metabolic requirements of both fetus and trophoblast are likely to be altered.…”

“…The human placental syncytiotrophoblast has been shown to possess Na+/H+ exchanger activity, with that on the MVM resembling the NHE-1 isoform, whereas the basal membrane exchanger resembles the NHE-2 isoform ( 13). The NHE-1 isoform is postulated to be associated with "housekeeping" functions such as cellular pH regulation (13).…”

Activity and Expression of the Na+/H+ Exchanger in the Microvillous Plasma Membrane of the Syncytiotrophoblast in Relation to Gestation and Small for Gestational Age Birth

“…To understand the relationship between the activity data and the NHE isoform expression data, one needs to know the relative contributions of the activities of the three NHE isoforms to total Na ϩ /H ϩ exchange across the MVM and also whether the activities of each isoform change with gestation. Kulanthaival et al (6) have suggested, using pharmacological techniques, that the NHE1 isoform is the predominant functioning isoform in Na ϩ /H ϩ exchange across the MVM. The amiloride concentration used in the present study would be sufficient to inhibit all three NHE isoforms.…”