ACUTE MODULATION OF INTESTINAL MRP2 ACTIVITY BY NUTRIENTS. INVOLVEMENT OF GLP-2

TOCCHETTI, GUILLERMO N.; DOMÍNGUEZ, CAMILA J.; ZECCHINATI, FELIPE; ARANA, MAITE R.; RIGALLI, JUAN P.; RUIZ, MARÍA L.; VILLANUEVA, SILVINA S. M.; MOTTINO, ALDO D.

MAR DEL PLATA

Congreso; REUNIÓN CONJUNTA SAIC SAI SAFIS 2018; 2018

Multidrug resistance-associated protein 2 (MRP2) is an ATP-dependent transporter expressed at the brush border membrane (BBM) of the enterocyte. It confers protection against absorption of toxicants from foods or bile. We recently demonstrated that MRP2 localization is subjected to a dynamic equilibrium between BBM and intracellular domains, thus allowing for rapid regulation of its function. Now we hypothesize that this acute MRP2 regulation takes place after intake of certain nutrients. The aims of this work were i) to evaluate whether this regulation takes place in vivo by effect of nutrients incorporated into the intestinal lumen and ii) to identify the underlying mechanism. Nutrient-containing preparations were incorporated into distal jejunum of fasted rats.Thirty min later, MRP2 activity was evaluated by quantifying efflux of the model substrate dinitrophenyl-S-glutathione into the apical compartment of proximal jejunum along a 30-min period. As result, we found a selective effect of nutrients with oleic acid (10% V/V) and glucose (100 mM) leading to significant increases in MRP2 activity (+202% ± 22% and +188% ± 45%, respectively; p