+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

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



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



Current Pharmaceutical Design 18(10): 1345-1371



The Na⁺/H⁺-exchanger 1, NHE1 (SLC9A1) and the electroneutral Na⁺,HCO₃⁻ cotransporter NBCn1 (SLC4A7) are coexpressed 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.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 055003347

Download citation: RISBibTeXText

PMID: 22360557


Related references

The acid-base transport proteins NHE1 and NBCn1 regulate cell cycle progression in human breast cancer cells. Cell Cycle 17(9): 1056-1067, 2018

Similarities and differences in the physiology and pharmacology of cat and rabbit carotid bodies. Federation Proceedings 39(9): 2653-2656, 1980

The Na/Hexchanger NHE1, but not the Na,HCO3cotransporter NBCn1, regulates motility of MCF7 breast cancer cells expressing constitutively active ErbB2. 2011

NBCn1 and NHE1 expression and activity in DeltaNErbB2 receptor-expressing MCF-7 breast cancer cells: contributions to pHi regulation and chemotherapy resistance. Experimental Cell Research 316(15): 2538-2553, 2010

The Na+/H+ exchanger NHE1, but not the Na+, HCO3(-) cotransporter NBCn1, regulates motility of MCF7 breast cancer cells expressing constitutively active ErbB2. Cancer Letters 317(2): 172-183, 2012

Redox Biology of Hydrogen Sulfide: Implications for Physiology, Pathophysiology, and Pharmacology. Redox Biology 1(1): 32-39, 2013

Asthma and COPD: Similarities and Differences in the Pathophysiology, Diagnosis and Therapy. Advances in Experimental Medicine and Biology 910: 31-38, 2017

Membrane permeability. Epithelial transport proteins: physiology and pathophysiology. Current Opinion in Cell Biology 10(4): 429-434, 1998

Anchoring of aquaporin-4 in brain: molecular mechanisms and implications for the physiology and pathophysiology of water transport. Neuroscience 129(4): 999, 2004

Physiology of sarcopenia. Similarities and differences with neoplasic cachexia (muscle impairments in cancer and ageing). Nutricion Hospitalaria 21(Suppl. 3): 38-45, 2006

The net acid extruders NHE1, NBCn1 and MCT4 promote mammary tumor growth through distinct but overlapping mechanisms. International Journal of Cancer 142(12): 2529-2542, 2018

Extracellular acidosis and very low [Na + ] inhibit NBCn1- and NHE1-mediated net acid extrusion from mouse vascular smooth muscle cells. Acta Physiologica 221(2): 129-141, 2017

The physiology and pathophysiology of rapamycin resistance: implications for cancer. Cell Cycle 10(7): 1050-1058, 2011

The intracellular distal tail of the Na+/H+ exchanger NHE1 is intrinsically disordered: implications for NHE1 trafficking. Biochemistry 50(17): 3469-3480, 2011

Fatty acid transport proteins, implications in physiology and disease. Biochimica et Biophysica Acta 1821(5): 852-857, 2012