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Discovery of Small Molecule Renal Outer Medullary Potassium (ROMK) Channel Inhibitors: A Brief History of Medicinal Chemistry Approaches To Develop Novel Diuretic Therapeutics.

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The renal outer medullary potassium (ROMK) channel is a member of the inwardly rectifying family of potassium (Kir, Kir1.1) channels. It is primarily expressed in two regions of the kidney, the cortical collecting duct (CCD) and the thick ascending loop of Henle (TALH). At the CCD it tightly

Immunolocalization of hyperpolarization-activated cationic HCN1 and HCN3 channels in the rat nephron: regulation of HCN3 by potassium diets.

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Hyperpolarization-activated cationic and cyclic nucleotide-gated channels (HCN) comprise four homologous subunits (HCN1-HCN4). HCN channels are found in excitable and non-excitable tissues in mammals. We have previously shown that HCN2 may transport ammonium (NH4 (+)), besides sodium (Na(+)), in the

Impaired renal NaCl absorption in mice lacking the ROMK potassium channel, a model for type II Bartter's syndrome.

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ROMK is an apical K(+) channel expressed in the thick ascending limb of Henle (TALH) and throughout the distal nephron of the kidney. Null mutations in the ROMK gene cause type II Bartter's syndrome, in which abnormalities of electrolyte, acid-base, and fluid-volume homeostasis occur because of

Effects of the potassium channel blocker barium on sodium and potassium transport in the rat loop of Henle in vivo.

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In vitro evidence suggests that the 'recycling' of K(+) ions through luminal K(+) channels in the thick ascending limb of the loop of Henle (TALH) is essential for the normal operation of the luminal Na(+)-K(+)-2Cl(-) co-transporter. In the present study these channels were investigated in vivo by

Luminal signal in tubuloglomerular feedback: what about potassium?

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Evidence suggests that a minimal luminal [K+] is required to elicit a full tubuloglomerular feedback (TGF) response, consistent with transmission of the TGF signal across the macula densa (MD) via the Na+-2Cl(-)-K+ cotransporter. Furthermore, it appears that luminal [K+] at the MD is close to the K+

Paradoxical body and kidney growth in potassium deficiency.

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In the growing animal, K deficiency (KD) retards body growth, but paradoxically stimulates renal growth. If KD persists, interstitial infiltrates appear and eventually tubulointerstitial fibrosis develops. In patients with chronic KD, renal cysts may form and with time tubulointerstitial disease

Effects of sodium artesunate, a new antimalarial drug, on renal function.

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BACKGROUND Sodium artesunate is currently used in malaria treatment. Adverse effects of this drug have not been described, probably because they cannot be differentiated from malaria-related effects. METHODS The effects on renal function of an acute infusion of sodium artesunate (12 mg/kg body

Characterization of aldose reductase from the thick ascending limb of Henle's loop of rabbit kidney.

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BACKGROUND The organic osmolyte sorbitol plays an important role in the osmoregulation of immortalized epithelial cells of the thick ascending limb of Henle's loop (TALH) of rabbit. The intracellular sorbitol content seems to depend strongly on the extracellular osmolarity. To investigate the nature

Silicon supplementation modulates antioxidant system and osmolyte accumulation to balance salt stress in Acacia gerrardii Benth.

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Experiments were conducted to investigate the role of silicon (Si, 2 mM potassium silicate - K₂SiO₃) in ameliorating the salinity (200 mM NaCl) triggered growth retardation, photosynthetic inhibition and the oxidative damage in Talh trees (Acacia gerrardii Benth).

Preliminary phytochemical and elemental analysis of aqueous and fractionated pod extracts of Acacia nilotica (Thorn mimosa).

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Acacia nilotica (Thorn mimosa) is used locally for various medicinal purposes by traditionalists and herbalists in northeastern Nigeria. Plants products have been used since ancient times in the management of various conditions. The bark of A. nilotica has been reported to be used traditionally to

Renal tubular chloride and renin release.

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We have suggested that the renal tubular signal for renin release is related to alterations of sodium chloride cotransport in the TALH. Renin release is inhibited by increased sodium chloride transport and stimulated by interrupted sodium chloride transport. Because of the different affinities of

The use of membrane vesicles to study the NaCl/KCl cotransporter involved in active transepithelial chloride transport.

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Properties of the NaCl/KCl cotransport system were investigated in isolated membranes by flux measurements and binding studies. Chloride competes with "furosemide-like loop diuretics" for its two binding sites at the cotransporter as evidenced by the decrease in piretanide sensitivity of sodium flux

Localization of diuretic effects along the loop of Henle: an in vivo microperfusion study in rats.

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In order to clarify the effects on sodium reabsorption in the loop of Henle of methazolamide (a carbonic anhydrase inhibitor), chlorothiazide and the loop diuretics frusemide and bumetanide, superficial loops were perfused in vivo in anaesthetized rats and the individual diuretics were included in

Dysfunction of the thick loop of Henle and senescence: from molecular biology to clinical geriatrics.

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The sodium-potassium-2 chloride bumetanide-sensitive transporter (NKCC2), a protein coded by gene SLC12A1, allows salt reabsorption in the thick ascending loop of Henle (TALH). The functional and clinical exploration of the TALH can be carried out using the Chaimowitz's test, which is based on the

Active chloride transport in rabbit thick ascending limb of Henle's loop and elasmobranch rectal gland: chloride fluxes in isolated plasma membranes.

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To investigate directly whether a sodium-potassium-chloride cotransport system is operating in the mammalian thick ascending limb of Henle's loop (TALH) and in the elasmobranch rectal gland, plasma membrane vesicles were prepared from TALH cells isolated from rabbit kidney outer medulla and from

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