ABC transporters in extrahepatic tissues: Pharmacological regulation in heart and intestine

VILLANUEVA, SILVINA; MOTINO, ALDO; ZHANG, WEI; VORE, MARY; ZHANG, WEI; VORE, MARY; ZECCHINATI, FELIPE; ZECCHINATI, FELIPE; VILLANUEVA, SILVINA; MOTINO, ALDO

CURRENT MEDICINAL CHEMISTRY.

BENTHAM SCIENCE PUBL LTD

Año: 2019 vol. 25

0929-8673

ATP binding cassette (ABC) transporters are transmembrane proteins expressed in secretory epithelia like the liver, kidneys and intestine, in epithelia exhibiting barrier function such as the blood-brain barrier and placenta, and to a much lesser extent, in tissues like reproductive organs, lungs, heart and pancreas, among others. They regulate internal distribution of endogenous metabolites and xenobiotics including drugs of therapeutic use and also participate in their elimination from the body. We here describe the function and regulation of ABC transporters in heart and small intestine, as examples of extrahepatic tissues, in which ABC proteins play clearly different roles. In heart, they are involved in tissue pathogenesis as well as in protecting this organ against toxic compounds and drug-induced oxidative stress. The small intestine is highly exposed to therapeutic drugs taken orally and, consequently, ABC transporters localized on its surface strongly influence drug absorption and pharmacokinetics. Examples of the ABC proteins currently described are Multidrug Resistance-associated Proteins 1 and 2 (MRP1 and 2) for heart and small intestine, respectively, and P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) for both organs.