Na+-Dependent Uptake of 4-Azidophenylalanine by Pig Intestinal Microvillus Vesicles. Interaction with Neutral Amino Acid Uptake and Labelling Pattern

Pathways of neutral amino acid uptake were investigated in vitro during differentiation of primary cultures of trophoblast isolated from full-term human placentas and a clone (b30) of the BeWo cell line. Inhibition of initial alanine (0.1 microM) uptake by 2-(methylamino)isobutyric acid and unlabeled alanine revealed two Na(+)-dependent systems and one Na(+)-independent transporter. Characterization of these transporters, by selective inhibition, suggested system A, ASC, and L-like transporters. Concomitant with formation of microvillous membrane and syncytium, system ASC activity decreased from 16.1 +/- 2.8 pmol.mg DNA-1.min-1 at 24 h to 2.4 +/- 1.1 pmol.mg DNA-1.min-1 at 72 h. Na(+)-independent alanine uptake increased from 6.0 +/- 2.0 to 12.9 +/- 0.9 pmol.mg DNA-1.min-1 at 24 and 72 h, respectively. Similarly, alpha-(methylamino)isobutyric acid-insensitive, Na(+)-dependent activity in b30 cells (100 microM alanine) decreased from 6.5 +/- 1.6 to 1.2 +/- 1.2 nmol.mg DNA-1.min-1 for control and forskolin-treated cells, respectively. We conclude that membrane specialization accompanying fusion and differentiation of the cytotrophoblast to form syncytiotrophoblast results in a polarization of neutral amino acid transport systems.

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Different mechanisms for neutral amino acid uptake by new-born pig colon

The Journal of Physiology ◽

10.1113/jphysiol.1979.sp012632 ◽

1979 ◽

Vol 286 (1) ◽

pp. 479-490 ◽

Cited By ~ 26

Author(s):

F. V. Sepúlveda ◽

M. W. Smith

Keyword(s):

Amino Acid ◽

Amino Acid Uptake ◽

Neutral Amino Acid ◽

Acid Uptake ◽

New Born

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Effect of Aspartame-Derived Phenylalanine on Neutral Amino Acid Uptake in Human Brain: A Positron Emission Tomography Study

Journal of Neurochemistry ◽

10.1111/j.1471-4159.1991.tb02047.x ◽

1991 ◽

Vol 56 (5) ◽

pp. 1526-1535 ◽

Cited By ~ 12

Author(s):

Robert A. Koeppe ◽

Barry L. Shulkin ◽

Karen C. Rosenspire ◽

Leslie A. Shaw ◽

A. Lords Betz ◽

...

Keyword(s):

Positron Emission Tomography ◽

Amino Acid ◽

Human Brain ◽

Amino Acid Uptake ◽

Neutral Amino Acid ◽

Emission Tomography ◽

Positron Emission Tomography Study ◽

Acid Uptake ◽

Positron Emission

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Vasoactive Intestinal Peptide induces glucose and neutral amino acid uptake through mTOR signalling in human cytotrophoblast cells

Scientific Reports ◽

10.1038/s41598-019-53676-3 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Fatima Merech ◽

Elizabeth Soczewski ◽

Vanesa Hauk ◽

Daniel Paparini ◽

Rosanna Ramhorst ◽

...

Keyword(s):

Amino Acid ◽

Vasoactive Intestinal Peptide ◽

Amino Acid Uptake ◽

Nutrient Sensing ◽

Neutral Amino Acid ◽

Acid Uptake ◽

Dependent Manner ◽

System A ◽

Cytotrophoblast Cells ◽

Mtor Signalling

AbstractThe transport of nutrients across the placenta involves trophoblast cell specific transporters modulated through the mammalian target of rapamycin (mTOR). The vasoactive intestinal peptide (VIP) has embryotrophic effects in mice and regulates human cytotrophoblast cell migration and invasion. Here we explored the effect of VIP on glucose and System A amino acid uptake by human trophoblast-derived cells (Swan 71 and BeWo cell lines). VIP activated D-glucose specific uptake in single cytotrophoblast cells in a concentration-dependent manner through PKA, MAPK, PI3K and mTOR signalling pathways. Glucose uptake was reduced in VIP-knocked down cytotrophoblast cells. Also, VIP stimulated System A amino acid uptake and the expression of GLUT1 glucose transporter and SNAT1 neutral amino acid transporter. VIP increased mTOR expression and mTOR/S6 phosphorylation whereas VIP silencing reduced mTOR mRNA and protein expression. Inhibition of mTOR signalling with rapamycin reduced the expression of endogenous VIP and of VIP-induced S6 phosphorylation. Our findings support a role of VIP in the transport of glucose and neutral amino acids in cytotrophoblast cells through mTOR-regulated pathways and they are instrumental for understanding the physiological regulation of nutrient sensing by endogenous VIP at the maternal-foetal interface.

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