The macula densa expresses a luminal Na(+)-K(+)-2Cl(-) cotransporter and a basolateral Cl(-) conductance. Although it is known that cotransport of Na(+), K(+), and Cl(-) is the first step in tubuloglomerular feedback (TGF), subsequent steps are unclear. We hypothesized that Na(+)-K(+)-2Cl(-) entry via the luminal Na(+)-K(+)-2Cl(-) cotransporter elevates intracellular Cl(-), increases electrogen...

The functional properties of alternatively spliced isoforms of the mouse apical Na+-K+-2Cl-cotransporter (mBSC1) were examined, using expression in Xenopus oocytes and measurement of22Na+or86Rb+uptake. A total of six isoforms, generated by the combinatorial association of three 5' exon cassettes (A, B, and F) with two alternative 3' ends, are expressed in mouse thick ascending limb (TAL) [see c...

The excretory system of insects consists of the Malpighian tubules and hindgut. The tubules secrete fluid by generation of a transepithelial osmotic gradient, which results from the active transport of Na+, K+ and Cl– into the lumen (Phillips, 1981). This primary urine is modified in the lower (proximal) Malpighian tubule and/or the rectum by reabsorption of useful molecules and water. The phys...

NaCl hyperosmolarity increases intestinal blood flow during food absorption due in large part to increased NO production. We hypothesized that in vivo, sodium ions enter endothelial cells during NaCl hyperosmolarity as the first step to stimulate an increase in intestinal endothelial NO production. Perivascular NO concentration ([NO]) and blood flow were determined in the in vivo rat intestinal...

Transport processes along the nephron are regulated in part by hormone stimulation of adenylyl cyclases mediated by the heterotrimeric G protein Gs. To assess the role of this pathway in the regulation of Na-K-2Cl cotransporter abundance in the renal thick ascending limb (TAL), we studied mice with heterozygous disruption of the G nas gene, which codes for the α-subunit of Gs. Outer medullary G...

ATP-sensitive potassium channels (K(ATP)) in the thick ascending limb of the loop of Henle play an important role in apical K(+) recycling, a mechanism essential for maintaining the activity of the Na/2Cl/K-cotransporter. We have previously demonstrated that inhibition of K(ATP) decreases Na(+) and K(+) absorption in the loop of Henle and induces diuretic and natriuretic effects. In the present...

In a previous study, we found that Na(+)-K(+)-2Cl(-) cotransporter in immature cortical neurons was stimulated by activation of the ionotropic N-methyl-D-aspartate (NMDA) glutamate receptor in a Ca(2+)-dependent manner. In this report, we investigated whether the Na(+)-K(+)-2Cl(-) cotransporter in immature cortical neurons is stimulated by non-NMDA glutamate receptor-mediated signaling pathways...

The bumetanide-sensitive component of pHi recovery from an NH4Cl-induced acute alkaline load was used as a measure of Na(+)-K(+)-2Cl- cotransport activity in rat parotid acini. Acinar treatment with NaF/AlCl3 (15 mM NaF plus 10 microM AlCl3) induced a 5-fold stimulation in the initial rate of bumetanide-sensitive pHi recovery. This effect was dependent on NaF concentration (K1/2 approximately 7...

A high-fructose diet is shown to induce salt-sensitive hypertension, but the underlying mechanism largely remains unknown. The major goal of the present study was to test the role of renal (pro)renin receptor (PRR) in this model. In Sprague-Dawley rats, high-fructose intake increased renal expression of full-length PRR, which were attenuated by allopurinol. High-fructose intake also upregulated...

Semiquantitative immunoblotting was used to investigate the expression levels of the four major renal aquaporins, the Na-K-2Cl cotransporter of the thick ascending limb, the type 3 Na-H exchanger, and the Na-K-ATPase in kidneys from rats with cirrhosis secondary to common bile duct ligation (CBDL). These rats had significant water retention and hyponatremia. In contrast to models of cirrhosis i...