NDLI: Mechanism of Na-K-ATPase Inhibition by PGE2 in Intestinal Epithelial Cells

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Mechanism of Na-K-ATPase Inhibition by PGE2 in Intestinal Epithelial Cells

Content Provider	MDPI
Author	Nepal, Niraj Arthur, Subha Haynes, Jennifer Palaniappan, Balasubramanian Sundaram, Uma
Copyright Year	2021
Description	The primary means of intestinal absorption of nutrients by villus cells is via Na-dependent nutrient co-transporters located in the brush border membrane (BBM). These secondary active co-transport processes require a favorable transcellular Na gradient that is provided by Na-K-ATPase. In chronic enteritis, malabsorption of essential nutrients is partially due to inhibition of villus Na-K-ATPase activity mediated by specific immune inflammatory mediators that are known to be elevated in the inflamed mucosa. However, how Prostaglandin E2 (PGE2), a specific mediator of nutrient malabsorption in the villus BBM, may mediate the inhibition of Na-K-ATPase is not known. Therefore, this study aimed to determine the effect of PGE2 on Na-K-ATPase in villus cells and define its mechanism of action. In vitro, in IEC-18 cells, PGE2 treatment significantly reduced Na-K-ATPase activity, accompanied by a significant increase in the intracellular levels of cyclic Adenosine Monophosphate (cAMP). The treatment with cAMP analog 8-Bromo-cAMP mimicked the PGE2-mediated effect on Na-K-ATPase activity, while Rp-cAMP (PKA inhibitor) pretreatment reversed the same. The mechanism of inhibition of PGE2 was secondary to a transcriptional reduction in the Na-K-ATPase α1 and β1 subunit genes, which was reversed by the Rp-cAMP pretreatment. Thus, the PGE2-mediated activation of the PKA pathway mediates the transcriptional inhibition of Na-K-ATPase activity in vitro.
Starting Page	752
e-ISSN	20734409
DOI	10.3390/cells10040752
Journal	Cells
Issue Number	4
Volume Number	10
Language	English
Publisher	MDPI
Publisher Date	2021-03-29
Access Restriction	Open
Subject Keyword	Cells Endocrinology and Metabolism Immunology Pge2 Intestinal Epithelial Cells Villus Na-k-atpase
Content Type	Text
Resource Type	Article

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