Abstract
The lung neuroendocrine system secretes a variety of peptides and biogenic amines in the alveolar space as well as in the surrounding tissues. Among them, serotonin has been shown to interfere with sodium transport in airways of different animal models. In this study, we investigated the effects of serotonin in human A549 and H441 adenocarcinoma cell lines. In patch-clamp whole-cell configuration, apical perfusion of serotonin (4mM and 2mM) induced an immediate and strong inhibition (70% and 45% respectively) of amiloride sensitive currents. The kinetics of inhibition suggests a direct interaction with the sodium transport protein ENaC. RTQ-PCR showed the presence of 5HT2b receptor mRNA. This receptor is linked to the phosphoinositide hydrolysis pathway. Therefore, we performed intracellular calcium measurements in Fura-2AM loaded H441 and A549 cells. These experiments showed a rapid 8–10% increase of the 340/380 epifluorescence ratio in response to 1mM apical serotonin. The A6 renal model of amiloride sensitive transport was used in parallel to investigate the putative effect basolateral serotonin. Transepithelial measurements showed an immediate and short-lived apical effect while basolateral serotonin induced a progressive inhibition of the current which was sustained for more than 90 minutes and lead to 80% inhibition of the current. Thus, serotonin inhibits independently apical and basolateral Na transport pathways through distinct mechanisms. AG is a FNRS doctoral fellow. This work was funded by grants from ULB and Fonds Defay.
Published Version
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