Journalartikel

Jahr der Veröffentlichung: 2024

Zeitschrift: European Journal of Pharmacology

Bandnummer: 982

ISSN: 0014-2999

eISSN: 1879-0712

Open Access Status: Hybrid

DOI Link: https://doi.org/10.1016/j.ejphar.2024.176941

Verlag: Elsevier

Abstract: 

ATP, released e.g. after cell damage or during inflammation, can alter ion transport across the intestinal mucosa via stimulation of purinergic receptors in the basolateral as well as in the apical membrane of epithelial cells. When ATP acts from the serosal side, it induces an increase in short-circuit current (Isc) sc ) via Cl-secretion- secretion across the colonic epithelium. In contrast, mucosal ATP or its derivative, BzATP, predominantly stimulating ionotropic P2X4 4 and P2X7 7 receptors, evoke an increase in Isc, sc , which could not be explained by Cl-- secretion. The underlying ion currents after stimulation of apical purinergic receptors in rat distal colon are still unclear and were investigated in the present study. Ussing chamber experiments revealed that the I sc induced by mucosal ATP was dependent on the presence of mucosal Ca2+ 2+ and inhibited by the K+ + channel blocker, Ba2+, 2+ , indicating the involvement of Ca2+-dependent 2+-dependent K+ + channels. Blockade of the transepithelial I sc by lanthanides (La3+, 3+ , Gd3+) 3+ ) suggests that Ca2+ 2+ enters the epithelium via nonselective cation channels. Experiments with basolaterally depolarized epithelia confirmed the activation of apical lanthanide-sensitive Na+- +- and Ca2+-permeable 2+-permeable cation channels by ATP. Putative candidates might be TRP channels, from which several subtypes were detected in colonic tissue in RT-PCR experiments. In addition, the activation of an apical Cl-- conductance was observed when suitable Cl-- concentration gradients were applied. Consequently, mucosal ATP, acting as 'danger signal', stimulates cation and anion channels in the apical membrane to induce a secretory response as part of the local defence mechanism in the intestinal epithelium.

Harvard-Zitierstil: Ballout, J. and Diener, M. (2024) Purinergic control of apical ion conductance by luminal ATP in rat colonic epithelium, European Journal of Pharmacology, 982, Article 176941. https://doi.org/10.1016/j.ejphar.2024.176941

APA-Zitierstil: Ballout, J., & Diener, M. (2024). Purinergic control of apical ion conductance by luminal ATP in rat colonic epithelium. European Journal of Pharmacology. 982, Article 176941. https://doi.org/10.1016/j.ejphar.2024.176941