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Volume 22
Issue 12
10.3390/ijms22126244
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Article

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

by
Alejandro Ogazon del Toro
,
Lidia Jimenez
,
Mauricio Serrano Rubi
,
Marcelino Cereijido
and
Arturo Ponce
*
Department of Physiology, Biophysics and Neurosciences, CINVESTAV-IPN, Mexico City 07360, Mexico
*
Author to whom correspondence should be addressed.
Academic Editor: Camillo Peracchia
Int. J. Mol. Sci. 2021, 22(12), 6244; https://doi.org/10.3390/ijms22126244
Received: 11 May 2021 / Revised: 28 May 2021 / Accepted: 4 June 2021 / Published: 10 June 2021
(This article belongs to the Special Issue Chemical Regulation of Gap Junction Channels and Hemichannels 2.0)
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Abstract

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. View Full-Text
Keywords: ouabain; gap junctions; dye transfer; prostaglandin E2 ouabain; gap junctions; dye transfer; prostaglandin E2
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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MDPI and ACS Style

Ogazon del Toro, A.; Jimenez, L.; Serrano Rubi, M.; Cereijido, M.; Ponce, A. Ouabain Enhances Gap Junctional Intercellular Communication by Inducing Paracrine Secretion of Prostaglandin E2. Int. J. Mol. Sci. 2021, 22, 6244. https://doi.org/10.3390/ijms22126244

AMA Style

Ogazon del Toro A, Jimenez L, Serrano Rubi M, Cereijido M, Ponce A. Ouabain Enhances Gap Junctional Intercellular Communication by Inducing Paracrine Secretion of Prostaglandin E2. International Journal of Molecular Sciences. 2021; 22(12):6244. https://doi.org/10.3390/ijms22126244

Chicago/Turabian Style

Ogazon del Toro, Alejandro, Lidia Jimenez, Mauricio Serrano Rubi, Marcelino Cereijido, and Arturo Ponce. 2021. "Ouabain Enhances Gap Junctional Intercellular Communication by Inducing Paracrine Secretion of Prostaglandin E2" International Journal of Molecular Sciences 22, no. 12: 6244. https://doi.org/10.3390/ijms22126244

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