Dynamic recycling of extracellular ATP in human epithelial intestinal cells

SAFFIOTI N; CL ALVAREZ; Z BAZZI; MV GENTILINI; G GONDOLESI; PJ SCHWARZBAUM ; J SCHACHTER

PLOS COMPUTATIONAL BIOLOGY

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2023

1553-734X

Intestinal epithelial cells play important roles in the absorption of nutrients, electrolytes secretion and food digestion. The function of these cells is strongly influenced by purinergic signalling activated by extracellular ATP (eATP) and other nucleotides. The activity of several ecto-enzymes determines the dynamic regulation of eATP.In this study, we characterized the dynamics of eATP on Caco-2 cells. Results show that non-polarized Caco-2 cells triggered a strong but transient release of intracellular ATP after hypotonic stimuli, leading to low micromolar eATP accumulation. Subsequent eATP hydrolysis mainly determined eATP decay, though this effect could be counterbalanced by eATP synthesis by ecto-kinases kinetically characterized in this study.In polarized Caco-2 cells, eATP showed a faster turnover at the apical- vs the basolateral side, where the unequal contribution of ecto-enzymes to eATP regulation was assessed. A data-driven model allowed to quantify and predict the contribution of each ecto-enzyme to eATP regulation.Experiments using human intestinal epithelial cells confirmed the presence of functional ecto-kinases promoting eATP synthesis. The adaptive value of eATP regulation and purinergic signalling in the intestine is discussed.