Physiology, pharmacology and pathophysiology of the pH regulatory transport proteins NHE1 and NBCn1: similarities, differences, and implications for cancer therapy

TY - JOUR

T1 - Physiology, pharmacology and pathophysiology of the pH regulatory transport proteins NHE1 and NBCn1

T2 - similarities, differences, and implications for cancer therapy

AU - Bødtkjer, Ebbe

AU - Bunch, Lennart

AU - Pedersen, Stine Helene Falsig

PY - 2012/4

Y1 - 2012/4

N2 - The Na+/H+-exchanger 1, NHE1 (SLC9A1) and the electroneutral Na+, HCO3--cotransporter NBCn1 (SLC4A7) are co-expressed in a wide range of tissues. Under normal physiological conditions these transporters play an ostensibly similar role, namely that of net acid extrusion after cellular acidification. In addition, they have been implicated in multiple other cellular processes, including regulation of transepithelial transport, cell volume, cell death/survival balance, and cell motility. In spite of their apparent functional similarity, the two transporters also serve distinctly different functions and are differentially regulated. Here, we provide an update on the basic structure, function, regulation, physiology and pharmacology of NHE1 and NBCn1, with particular focus on the factors responsible for their functional similarities and differences. Finally, we highlight recent findings implicating these transporters in cancer development, and discuss issues relating to NHE1 and NBCn1 as potential targets in cancer treatment.

AB - The Na+/H+-exchanger 1, NHE1 (SLC9A1) and the electroneutral Na+, HCO3--cotransporter NBCn1 (SLC4A7) are co-expressed in a wide range of tissues. Under normal physiological conditions these transporters play an ostensibly similar role, namely that of net acid extrusion after cellular acidification. In addition, they have been implicated in multiple other cellular processes, including regulation of transepithelial transport, cell volume, cell death/survival balance, and cell motility. In spite of their apparent functional similarity, the two transporters also serve distinctly different functions and are differentially regulated. Here, we provide an update on the basic structure, function, regulation, physiology and pharmacology of NHE1 and NBCn1, with particular focus on the factors responsible for their functional similarities and differences. Finally, we highlight recent findings implicating these transporters in cancer development, and discuss issues relating to NHE1 and NBCn1 as potential targets in cancer treatment.

M3 - Journal article

SN - 1381-6128

VL - 18

SP - 1345

EP - 1371

JO - Current Pharmaceutical Design

JF - Current Pharmaceutical Design

IS - 10

ER -