OSR1-sensitive small intestinal Na+ transport.

Pasham V, Pathare G, Fajol A, Rexhepaj R, Michael D, Pakladok T, Alesutan I, Rotte A, Foller M, Lang F. OSR1-sensitive small intestinal Na+ transport. Am J Physiol Gastrointest Liver Physiol 303: G1212-G1219, 2012. First published September 27, 2012; doi: 10.1152/ajpgi.00367.2011.-The oxidative stress responsive kinase 1 (OSR1) contributes to WNK (with no K)-dependent regulation of renal tubular salt transport, renal salt excretion, and blood pressure. Little is known, however, about a role of OSR1 in the regulation of intestinal salt transport. The present study thus explored whether OSR1 is expressed in intestinal tissue and whether small intestinal Na+/H+ exchanger (NHE), small intestinal Na+-glucose cotransport (SGLT1), and/or colonic epithelium Na+ channel (ENaC) differ between knockin mice carrying one allele of WNK-resistant OSR1 (osr1(+/KI)) and wild-type mice (osr1(+/+)). OSR1 protein abundance was determined by Western blotting, cytosolic pH from BCECF fluorescence, NHE activity from Na+-dependent realkalinization following an ammonium pulse, SGLT1 activity from glucose-induced current, and colonic ENaC activity from amiloride-sensitive transepithelial current in Ussing chamber experiments. As a result, OSR1 protein was expressed in small intestine of both osr1(+/KI) mice and osr1(+/+) mice. Daily fecal Na+, K+, and H2O excretion and jejunal SGLT1 activity were lower, whereas small intestinal NHE activity and colonic ENaC activity were higher in osr1(+/KI) mice than in osr1(+/+) mice. NHE3 inhibitor S-3226 significantly reduced NHE activity in both genotypes but did not abrogate the difference between the genotypes. Plasma osmolarity, serum antidiuretic hormone, plasma aldosterone, and plasma corticosterone concentrations were similar in both genotypes. Small intestinal NHE3 and colonic alpha-ENaC protein abundance were not significantly different between genotypes, but colonic phospho-beta-ENaC (ser633) was significantly higher in osr1(+/KI) mice. In conclusion, OSR1 is expressed in intestine and partial WNK insensitivity of OSR1 increases intestinal NHE activity and colonic ENaC activity.