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

Kulanthaivel, Palaniappan; Furesz, T.C.; Moe, A.J.; Smith, Carl H.; Mahesh, Virendra B.; Leibach, Frederick H.; Ganapathy, Vadivel

doi:10.1042/bj2840033

Cited by 38 publications

(32 citation statements)

References 28 publications

(50 reference statements)

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“…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).…”

Section: Na+-h+ Exchanger Activity and Fetal Growthmentioning

confidence: 99%

Placental transporter activity and expression in relation to fetal growth

Sibley¹,

Glazier²,

D'Souza³

1997

Experimental Physiology

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SUMMARYThe question of whether there are causative or compensatory changes in placental transport physiology affecting fetal growth is considered. Reductions in uterine and umbilical blood flow in growth retardation will reduce maternofetal exchange of lipophilic solutes, such as 02 and CO2, but will not have a major effect on the transfer of hydrophilic solutes. These solutes are transferred across the placenta by paracellular diffusion, transporter protein-mediated transport and endocytosis-exocytosis. Neither paracellular diffusion nor endocytosis-exocytosis has been investigated in relation to fetal growth. The weight of evidence is that there is no change in the activity and expression of the syncytiotrophoblast GLUT1 glucose transporter in fetal growth retardation. However, there is strong evidence that the activity of the system A amino acid transporter, per milligram of placental membrane protein, is altered in relation to fetal growth, but in a complex manner. There is also some weaker evidence that the activity of the Na+-H+ exchanger, per milligram of placental membrane protein, is directly related to birth-weight. There are no data for other solute transporters; a considerable amount of work still remains to be done in order to understand the relationship between placental function and fetal growth rate.

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“…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).…”

Section: Na+-h+ Exchanger Activity and Fetal Growthmentioning

confidence: 99%

Placental transporter activity and expression in relation to fetal growth

Sibley¹,

Glazier²,

D'Souza³

1997

Experimental Physiology

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“…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.…”

mentioning

confidence: 99%

“…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).…”

mentioning

confidence: 99%

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

Kuruvilla¹,

D'Souza²,

Glazier³

et al. 1994

J. Clin. Invest.

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Fetal macrosomia (FM) is a well-recognized complication of diabetic pregnancy but it is not known whether placental transport mechanisms are altered. We therefore studied the activity of the system A amino acid transporter, the system L amino acid transporter, and the Na+/H+ exchanger in microvillous membrane vesicles from placentas of macrosomic babies born to diabetic women (FM group), from placentas of appropriately grown babies born to diabetic women (appropriate for gestational age group) and from placentas of appropriately grown babies of normal women (control group). Sodium-dependent uptake of ["'C]-methylaminoisobutyric acid at 30 s (initial rate, a measure of system A activity) was 49% lower into FM vesicles than into control vesicles (P < 0.02); this effect was due to a decrease in Vmax of the transporter with no change in Km. There was no significant difference in system A activity between the appropriate for gestational age group and control or FM group. There was also no difference between system L transporter or Na+/H+ exchanger activity between the three groups. We conclude that the number of system A transporters per milligram of membrane protein in the placental microvillous membrane is selectively reduced in diabetic pregnancies associated with FM. (J. Clin. Invest. 1994.

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“…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.…”

Section: Placental Namentioning

confidence: 99%

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

et al. 2000

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The effect of gestational age, low birth weight, and umbilical plasma pH on the activity and expression of the Na ϩ /H ϩ exchanger in the microvillous plasma membrane (MVM) of the placental syncytiotrophoblast was investigated. MVM were isolated from placentas of fetuses delivered in the first and second trimesters and from appropriately grown for gestational age (AGA) and small for gestational age (SGA) babies born at term. 48 [0.92-1.66] nmol/mg protein/30s, respectively, n ϭ 6, 12, and 9). As regards exchanger isoforms, Western blotting showed that NHE1 expression did not change across gestation, but NHE2 and NHE3 expression were lower (p Ͻ 0.01) in the first and second trimesters than in term AGA MVM. There were no differences in Na ϩ /H ϩ exchanger activity or in NHE1-3 expression in term AGA MVM versus SGA (n ϭ 11) MVM. There was no correlation between exchanger activity and umbilical artery or vein plasma pH, although with a relatively small number of samples (n ϭ 12 and 15, respectively). We conclude that there is differential regulation of the activity and expression of Na Abbreviations SGA, small for gestational age MVM, microvillous plasma membrane BM, basal membrane IUGR, intrauterine growth restricted AGA, appropriately grown for gestational age SGAD, small for gestational age babies with abnormal systolic/diastolic ratios on umbilical Doppler ultrasound assessment.Fetal and neonatal acidemia are associated with intrapartum hypoxia, a known risk factor for poor neurologic outcome of affected babies (1). Fetal acidemia is more common in SGA babies, especially those with compromised umbilical artery blood flow (2, 3). The role of the placenta in regulating the pH of the fetus is not fully understood. Undoubtedly, proton and bicarbonate may be rapidly lost, or gained, across the placenta in the form of carbon dioxide and water. Furthermore, the placenta has a high paracellular permeability to hydrophilic solutes including ions (4, 5) so that simple diffusion of proton and bicarbonate via this route might also be important. In addition to this, Na ϩ /H ϩ and Cl Ϫ /HCO 3 Ϫ exchangers have been identified in the MVM and BM of the syncytiotrophoblast (6 -10), the transporting epithelium of the placenta. Although these might be involved in the homeostasis of intracellular syncytiotrophoblast pH, they also afford the possibility of a transcellular mechanism of transplacental transfer, which might contribute to fetal pH regulation. A role of the exchangers in either of these processes would provide a mechanism for acute, hormonal (e.g. epidermal growth factor, angiotensin II) control of H ϩ transport, by analogy to other tissues (11). The Na ϩ /H ϩ exchanger is found in most cells and contributes to intracellular pH homeostasis and, depending on the organ, transepithelial transport (11). Six different isoforms of this transport protein, designated NHE, have now been cloned and sequenced (11). Na

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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

Cited by 38 publications

References 28 publications

Placental transporter activity and expression in relation to fetal growth

Placental transporter activity and expression in relation to fetal growth

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

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

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