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Prostaglandin E2 induces upregulation of Na+ transport across Xenopus lung epithelium

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Abstract

The apical mucus on pulmonary epithelia is not only critical for physiological functions such as gas exchange or inflammatory processes, but also contains surfactants and multiple molecules that mediate cellular responses. A tight control of transepithelial ion transport maintains viscosity of this layer and, e.g., the amiloride-sensitive sodium channels (ENaCs) in lung epithelia of vertebrates are the most important regulatory sites for transcellular sodium uptake. Dysfunction of this sodium transport results in reduced liquid absorption and causes massive problems with gas exchange. We used dissected lungs of Xenopus laevis in Ussing chambers to investigate the influence of prostaglandin E2 (PGE2) on the regulation of short-circuit current (I SC) and amiloride-sensitive sodium absorption (I ami). Apical application of PGE2 (1 μM) increased I SC by 38% and I ami by approximately 60%. In contrast, a different prostaglandin, PGI2, neither affected I SC nor I ami. Forskolin increased current to a similar magnitude and preincubation of the lung with an RP-isomer of cyclic AMP, an inhibitor of proteinkinase A (PKA), abolished the effects of both PGE2 and forskolin. Transepithelial Na+ uptake was also upregulated by the prostaglandin receptor agonists misoprostol and sulprostone . The I ami in Xenopus oocytes that heterologously expressed ENaCs was not affected by PGE2.

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Abbreviations

ACTH:

adrenocorticotropic hormone

ENaC :

epithelial sodium channel

hENaC :

epithelial sodium channels from human lung

ORI :

oocyte Ringer’s solution

PKA :

protein kinase A

R T :

transepithelial resistance

V T :

transepithelial potential

xENaC :

epithelial sodium channels from Xenopus nephron

I ami :

amiloride-sensitive current

I SC :

short-circuit current

NRS :

normal Ringer’s solution

PGE 2 :

prostaglandin E2

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Acknowledgements

We thank Dr. P. Barbry (Nice) for kind supply of the human ENaC and Prof. Dr. F. Grimminger (Giessen) for providing PGI2. The excellent technical assistance of Sigfried Kristek and Bernhard Kahnert is greatly acknowledged. All experiments were performed in agreement with the German “laws of animal care”. The present study was supported by Stiftung VERUM.

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Correspondence to A. Berk.

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Communicated by G. Heldmaier

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Berk, A., Fronius, M., Clauss, W. et al. Prostaglandin E2 induces upregulation of Na+ transport across Xenopus lung epithelium. J Comp Physiol B 174, 83–89 (2004). https://doi.org/10.1007/s00360-003-0391-3

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