Prostaglandin E2 Enhances Gap Junctional Intercellular Communication in Clonal Epithelial Cells

Ouabain is a cardiac glycoside that has been described as a hormone, with interesting effects on epithelial physiology. We have shown previously that ouabain induces gap junctional intercellular communication (GJIC) in wild, sensitive cells (MDCK-S), but not in cells that have become insensitive (MDCK-I) by modifying their Na+-K+-ATPase. We have also demonstrated that prostaglandin E2 (PGE2) is able to induce increased GJIC by a mechanism other than ouabain, that does not depend on Na+-K+-ATPase. In this work we show, by dye transfer assays, that when MDCK-S and MDCK-I are randomly mixed, to form monolayers, the latter stablish GJIC, because of stimulation by a compound released to the extracellular media, by MDCK-S cells, after treatment with ouabain, as evidenced by the fact that monolayers of only MDCK-I cells, treated with a conditioned medium (CM) that is obtained after incubation of MDCK-S monolayers with ouabain, significantly increase their GJIC. The further finding that either (1) pre-treatment with COX-2 inhibitors or (2) addition to CM of antagonists of EP2 receptor abolish CM’s ability to induce GJIC in MDCK-I monolayers indicate that PGE2 is the GJIC-inducing compound. Therefore, these results indicate that, in addition to direct stimulation, mediated by Na+-K+-ATPase, ouabain enhances GJIC indirectly through the paracrine production of PGE2.

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Influence of Cardiac Glycosides and Prostaglandins on the Physiology of Epithelial Cells

Ponce¹,

Shoshani²,

Toro³

et al. 2023

Human Physiology - Annual Volume 2023 [Working Title]

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Epithelial cells play a major role in animal and human homeostasis because they selectively regulate the exchange of solutes between two given media, such as blood or urine. Cardiac glycosides (CG) are a group of highly toxic compounds whose best therapeutic known effect is on heart, although recent evidence has shown that it exerts a wide range of physiological effects on cells and tissues other than the heart. Prostaglandins, on the other hand, are a group of lipids that produce diverse physiological and pathological effects among which inflammation stands out. In this chapter, we describe that cardiac glycosides modulate key features of epithelial cell physiology, including cell-cell contact junctional complexes, cilliogenesis, and gap junction-mediated intercellular communication (GJIC) in epithelial cells. Prostaglandin PGE2 also modulates GJIC through a different signaling pathway. In addition, we describe that CG induce paracrine release of prostaglandin PGE2, which in turn modulates GJIC by itself.

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Prostaglandin E2 Enhances Gap Junctional Intercellular Communication in Clonal Epithelial Cells

Cited by 3 publications

References 106 publications

Remodeling the immune microenvironment for gastric cancer therapy through antagonism of prostaglandin E2 receptor 4

Remodeling the immune microenvironment for gastric cancer therapy through antagonism of prostaglandin E2 receptor 4

Ouabain Enhances Gap Junctional Intercellular Communication by Inducing Paracrine Secretion of Prostaglandin E2

Influence of Cardiac Glycosides and Prostaglandins on the Physiology of Epithelial Cells

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