Na-K-Cl cotransporter (NKCC2)-mediated sodium chloride reabsorption in the thick ascending limb is stimulated by the antidiuretic hormone vasopressin.



An overview of NKCC

NKCC (Na-K-Cl cotransporter) exists widely in different tissues of different animals and plays an extremely important physiological role, including maintaining and regulating cell volume and ion concentration as well as regulating cell growth and development. Studies have shown that NKCC1 plays an important role in cell cycle and clinicopathology in esophageal carcinoma. In addition, NKCC1 protein can improve the movement and diffusion speed of malignant glioma (brain cancer) cancer cells in brain tissue.

Major types of NKCC

There are two homologous isomers of Na-K-Cl cotransporter, NKCC1 and NKCC2. NKCC1, distributing in several tissues, including salivary gland, stomach, lung, trachea and pancreas. In almost all secretory epithelium, mRNA of NKCCl is also present in non-epithelial tissues. NKCC1 is composed of 1200 amino acid residues, and 58% of the amino acids are the same as NKCC2, which is smaller than NKCC1 subunit and consists of 1100 amino acid residues. The study showed that the NKCCl of mice was located on chromosome 18, while NKCC2 was located on chromosome 2. Human NKCCI is located on chromosome 5.

Inhibition of NKCC

There are three kinds of NKCC co-transporter channel inhibitors: Bumetanide, Furosemide (Lasix) and Furosemide sodium. Bumetanide (Ro 10-6338; PF 1593) is an inhibitor with an IC50 of 0.6 uM. Furosemide sodium (Lasix) is a loop diuretic inhibitor of NKCC, which is used in the treatment of congestive heart failure and edema.

NKCC and diseases

NKCC1 can promote the secretion of CI in intestinal epithelial cells through epidermal growth factor (EGF), and improve the ability of regulating intestinal interstitial fluid. NKCC1 can promote the proliferation and invasion of gliomas. NKCC1 protein also plays an important role in the occurrence and development of brain tumor. The expression of NKCC1 protein is positively correlated with the malignant degree of glioma. NKCC1 regulates the metastasis of glioma cells mainly through two different mechanisms. One is to regulate the dynamic of adhesion plaque and the tractive force of cells, the other is to regulate the cell volume by ion transport.


1. Li Bo, Meng Chao, Hu Shaoshan. Correlation between the expression of NKCC-1 and VEGF and peritumoral edema in meningiomas [J]. Modern Oncology 24 (08): 1200-1203.