Physiological and pathophysiological factors affecting the expression and activity of the drug transporter MRP2 in intestine.

ARANA, MAITE R; MOTTINO, ALDO D; RIGALLI, JUAN PABLO; TOCCHETTI, GUILLERMO N; VILLANUEVA, SILVINA SM

PHARMACOLOGICAL RESEARCH

ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2016 vol. 109 p. 32 - 44

1043-6618

The gastrointestinal epithelium functions as a selective barrier to absorb nutrients, electrolytes and water,but at the same time restricts the passage into the systemic circulation of intraluminal potentially toxiccompounds. This epithelium maintains its selective barrier function through the presence of very selec-tive and complex intercellular junctions and the ability of the absorptive cells to reject those compounds.Accordingly, the enterocytes metabolize orally incorporated xenobiotics and secrete the hydrophilicmetabolites back into the intestinal lumen through specific transporters localized apically. In the recentdecades, there has been increasing recognition of the existence of the intestinal cellular barrier. In thepresent review we focus on the role of the multidrug resistance-associated protein 2 (MRP2, ABCC2) inthe apical membrane of the enterocytes, as an important component of this intestinal barrier, as well as onits regulation. We provide a detailed compilation of significant contributions demonstrating that MRP2expression and function vary under relevant physiological and pathophysiological conditions. BecauseMRP2 activity modulates the availability and pharmacokinetics of many therapeutic drugs administeredorally, their therapeutic efficacy and safety may vary as well.