title: OSR1-sensitive small intestinal Na+ transport.
abstract: 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 H(2)O 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 α-ENaC protein abundance were not significantly different between genotypes, but colonic phospho-β-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.
authors.affiliation: Department of Physiology, University of Tübingen, Gmelinstr. 5, D-72076 Tübingen, Germany.
authors.forename: Venkanna
authors.initials: V
authors.lastname: Pasham
authors.forename: Ganesh
authors.initials: G
authors.lastname: Pathare
authors.forename: Abul
authors.initials: A
authors.lastname: Fajol
authors.forename: Rexhep
authors.initials: R
authors.lastname: Rexhepaj
authors.forename: Diana
authors.initials: D
authors.lastname: Michael
authors.forename: Tatsiana
authors.initials: T
authors.lastname: Pakladok
authors.forename: Ioana
authors.initials: I
authors.lastname: Alesutan
authors.forename: Anand
authors.initials: A
authors.lastname: Rotte
authors.forename: Michael
authors.initials: M
authors.lastname: Föller
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000818:Animals; D053503:Epithelial Sodium Channels / Q000378:metabolism; D055879:Gene Knock-In Techniques; D006146:Guanidines / Q000494:pharmacology; D008689:Methacrylates / Q000494:pharmacology; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051269:Sodium-Glucose Transporter 1 / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism
chemical_list: C118956:3-(2-(3-guanidino-2-methyl-3-oxo-propenyl)-5-methylphenyl)-N-isopropylidene-2-methyl-acrylamide dihydrochloride; D053503:Epithelial Sodium Channels; D006146:Guanidines; D008689:Methacrylates; C495675:Slc5a1 protein, mouse; D051269:Sodium-Glucose Transporter 1; D017923:Sodium-Hydrogen Exchangers; C534421:OXSR1 protein, mouse; D017346:Protein Serine-Threonine Kinases