Gastrointestinal distribution and kinetic characterization of the sodium-hydrogen exchanger isoform 8 (NHE8)

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
Hua XuFayez K Ghishan

Abstract

NHE8 is a newly identified NHE isoform expressed in rat intestine. To date, the kinetic characteristics and the intestinal segmental distribution of this NHE isoform have not been studied. This current work was performed to determine the gene expression pattern of the NHE8 transporter along the gastrointestinal tract, as well as its affinity for Na(+), H(+), and sensitivity to known NHE inhibitors HOE694 and S3226. NHE8 was differentially expressed along the GI tract. Higher NHE8 expression was seen in stomach, duodenum, and ascending colon in human, while higher NHE8 expression was seen in jejunum, ileum and colon in adult mouse. Moreover, the expression level of NHE8 is much higher in the stomach and jejunum in young mice compared with adult mice. To evaluate the functional characterictics of NHE8, the pH indicator SNARF-4 was used to monitor the rate of intra-cellular pH (pH(i)) recovery after an NH(4)Cl induced acid load in NHE8 cDNA transfected PS120 cells. The NHE8 cDNA transfected cells exhibited a sodium-dependent proton exchanger activity having a Km for pH(i) of approximately pH 6.5, and a Km for sodium of approximately 23 mM. Low concentration of HOE694 (1 microM) had no effect on NHE8 activity, while high concentrat...Continue Reading

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