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

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 (ISC) and amiloride-sensitive sodium absorption (Iami). Apical application of PGE2 (1 microM) increased ISC by 38% and Iami by approximately 60%. In contrast, a different prostaglandin, PGI2, neither affected ISC nor Iami. Forskolin increased current to a similar magnitude and preincubation of the lung with an RP-isomer of cyclic AMP, an inhibitor of protein kinase 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 Iami in Xenopus oocytes that heterologously expressed ENaCs was not affected by PGE2.