The role of Na+-H+ exchange in Na+ transport across the apical membrane was evaluated in Necturus gallbladder epithelium by means of intracellular Na+ activity (aNai) and 22Na+ uptake measurements. Under control conditions, complete replacement of Na+ in the mucosal solution with tetramethylammonium reduced aNai from 14.0 to 6.9 mM in 2 min (P less than 0.001). Mucosal addition of the Na+-H+ ex...

Bartter syndrome (BS) is a heterogeneous renal tubular disorder affecting Na-K-Cl reabsorption in the thick ascending limb of Henle's loop. BS type I patients typically present with profound hypokalemia and metabolic alkalosis. The main goal of the present study was to elucidate the functional implications of six homozygous mutations (G193R, A267S, G319R, A508T, del526N, and Y998X) in the bumet...

The tubular secretion of diuretics in the proximal tubule has been shown to be critical for the action of drugs. To elucidate the molecular mechanisms for the tubular excretion of diuretics, we have elucidated the interactions of human organic anion transporters (hOATs) with diuretics using cells stably expressing hOATs. Diuretics tested were thiazides, including chlorothiazide, cyclothiazide, ...

During development, neural networks progress through important functional changes such as the generation of spontaneous activity, the expression of a depolarizing chloride gradient, and the appearance of neuromodulation. Little is known about how these processes are integrated to yield mature behaviors. We showed previously that, during the maturation of the locomotor network of the zebrafish, ...

Bumetanide is a 3-aminobenzoic acid derivative. Of the several analogues having various substituents which are about equally active in test animals (3). Ostergaard elal. (5) selected 3-n-butylamino-4-phenoxy·5-sulphamyl benzoic acid (bumetanide) and studied its pharmacological properties. including its diuretic action in rats and dogs. Besides the diuretic effect bumetanide displayed hardly any...

NA -K -2CL COTRANSPORTERS (NKCCs) belong to the superfamily of Cl -coupled carriers and provide electroneutral symport of Na , K , and Cl . Two NKCC isoforms have been cloned from vertebrate cDNA libraries. NKCC2 is exclusively expressed in the apical membranes of thick ascending limb and macula densa and plays a major role in renal handling of salt and osmotically obliged water. In contrast, N...

This study describes efficacy of continuous infusion of bumetanide in severe congestive heart failure (CHF) associated with severe renal failure. Renal failure progresses as CHF advances. Renin-angiotensin inhibitor drugs consisting of angiotensin converting enzyme inhibitor and angiotensin receptor blocker are main stay of therapy in CHF. These drugs aggravate renal failure, decrease urine out...

To determine whether a K(+)-sensor mechanism exists in the hepatoportal region, periarterial hepatic afferent nerve activity responses to intraportal injection of KCl were examined in anesthetized rats. Hepatic afferent nerve activity increased in response to intraportal injection in a K(+) concentration-dependent manner, and the increase was attenuated by inhibition of the Na(+)-K(+)-2Cl(-) co...

Shimamoto C, Umegaki E, Katsu K, Kato M, Fujiwara S, Kubota T, Nakahari T. [Cl ]i modulation of Ca -regulated exocytosis in ACh-stimulated antral mucous cells of guinea pig. Am J Physiol Gastrointest Liver Physiol 293: G824–G837, 2007. First published August 2, 2007; doi:10.1152/ajpgi.00125.2007.—The effects of intracellular Cl concentration ([Cl ]i) on acetylcholine (ACh)-stimulated exocytosis...