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Bumetanide Inhibitor 99.91% Bumetanide (Ro 10-6338;PF 1593) is a selective Na +-K +-Cl-cotransporter 1 (NKCC1) inhibitor, weakly inhibits NKCC2, with IC 50 … Selective K + /Cl--cotransporter inhibitor. Furosemide is also a GABAA receptors antagonist and displays 100-fold selectivity for α6-containing receptors than α1-containing receptors. In a previous work, we have shown that overexpression of the Na+/K+/Cl− cotransporter (NKCC1) induces cell proliferation and transformation. Read "Potassium transport in nonpigmented epithelial cells of ocular ciliary body: Inhibition of a Na + , K + , Cl − cotransporter by protein kinase C, Journal of Cellular Physiology" on DeepDyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. Reactivity: Human Host: Rabbit Clone: Polyclonal 2 images | Order Na-K-Cl Cotransporter 2 antibody (ABIN2916308). Biemesderfer D, Payne J, Lytle C, Forbush B. Immunocytochemical studies of the Na-K-Cl cotransporter of shark kidney. Efficacy of novel NKCC1 (Na +-K -Cl− cotransporter 1) inhibitors in reducing ischemic infarction and cerebral edema in mice after transient middle cerebral artery occlusion (t-MCAO). Does not affect the bumetanide-sensitive Na + /K + /Cl--cotransport system. Purity > 98% CAS Number. A, Experimental protocol in normotensive mice and representative TTC (2,3,5-triphenyltetrazolium chloride) staining images. the sodium-potassium-chloride and potassium-chloride cotransporters are structurally related ion transport proteins that mediate electrically neutral transport of monovalent cations and Cl ions across plasma membranes (11, 20, 30).Two isoforms of each transporter have been cloned. View and buy high purity NKCC Cotransporter inhibitors from Tocris Bioscience. The Na-K-Cl cotransporter NKCC1 is widely expressed in mammalian tissue (4, 32), whereas NKCC2 is kidney … Furosemide acts as a loop diuretic and used for the study of congestive heart failure, hypertension and edema. Inhibition of Na-K-Cl cotransporter isoform 1 reduces lung injury induced by ischemia–reperfusion Chou-Chin Lan, MD, PhD,a,b Chung-Kan Peng, MD, ... IkB ¼ inhibitor of NF-kB IKK ¼ IkB kinase IR ¼ ischemia–reperfusion Kf ¼ microvascular permeability KNCC ¼ sodium-potassium-chloride co-transporter Na-K-Cl cotransport. We hypothesized that cation-dependent Cl- transport protein Na-K-Cl cotransporter isoform 1 (NKCC1) plays a role in the disruption of ion homeostasis in cerebral ischemia. In the current study, a role for NKCC1 in neuronal death was elucidated in neurotoxicity induced by glutamate and oxygen and glucose deprivation (OGD). In this study, we have used chimeras and point mutations to determine which transmembrane domains (tm's) are responsible for the differences in ion transport and in inhibitor binding kinetics. We recently found that ammonia, a key etiological factor in ALF, caused the activation of the Na-K-Cl cotransporter-1 (NKCC1) in cultured astrocytes, and that inhibition of such activation led to a reduction in astrocyte swelling, suggesting that NKCC1 activation may be an important factor in the mechanism of brain edema in ALF. Am J Physiol. It is most commonly marketed by Sanofi under the brand name Lasix, and also under the brand names Fusid and Frumex. The Na-K-Cl cotransporter (NKCC2) is the major salt transport pathway in the thick ascending limb of Henle's loop and is part of the molecular mechanism for blood pressure regulation. If the BBB Na-K-Cl cotransporter contributes to ischemia-induced edema formation, then edema should be attenuated or slowed by Na-K-Cl cotransporter inhibition. The Na +-K +-2Cl − cotransporter 1 (NKCC1) belongs to the solute carrier family 12 and provides electroneutral symport of sodium, potassium, and chloride. We hypothesized that high extracellular K + concentration ([K +] o)-mediated stimulation of Na +-K +-Cl − cotransporter isoform 1 (NKCC1) may result in a net gain of K + and Cl − and thus lead to high-[K +] o-induced swelling and glutamate release.In the current study, relative cell volume changes were determined in astrocytes. In this study, we compare the kinetic and regulatory behav-ior of NKCC1, h 1 r 2A 0.7, and the endogenous HEK cell cotrans-porter. The de-differentiated line does not ex-hibit epithelial characteristics, and it is therefore not possible to predict which isoform of Na-K-Cl cotransporter might be present. The effects of TNF gene deletion on renal Na +-K +-2Cl − cotransporter (NKCC2) expression and activity were determined. The Na+–K+–2Cl− cotransporter localized in the brain vascular endothelium has been shown to be important in the evolution of cerebral edema following experimental stroke. 13). NKCC-1 is the isoform of NKCC that is expressed ubiquitously in the brain and in other tissues; NKCC-2, the other isoform of this transporter, is expressed only in the kidney ( Russell, 2000 ). 81166-47-4 . To determine whether the Na-K-Cl cotransporter inhibitor bumetanide might reduce edema associated with DKA as it reduces edema in ischemic stroke, we administered bumetanide (30 mg/kg) intravenously to both control and DKA rats and determined cerebral ADC values. ... and a 3-fold higher affinity for the inhibitor bumetanide. The Na-K-Cl cotransporter (NKCC) is a protein that aids in the secondary active transport of sodium, potassium, and chloride into cells. J Biol Chem 278:52848–52856 In order to ascertain that the regulated and normal expression of the Na + /K + /Cl − cotransporter control cell proliferation, the effect of bumetanide a specific inhibitor of the cotransporter, was tested on Balb/c 3T3 cell proliferation, induced by fibroblasts growth factor (FGF) and fetal calf serum (FCS). Bumetanide (Ro 10-6338;PF 1593) is a selective Na +-K +-Cl-cotransporter 1 (NKCC1) inhibitor, weakly inhibits NKCC2, with IC 50 s of 0.68 and 4.0 μM for hNKCC1A and hNKCC2A, respectively. In humans there are two isoforms of this membrane transport protein, NKCC1 and NKCC2, encoded by two different genes (SLC12A2 and SLC12A1 respectively). 1996;270:F927-36 pubmed Lytle C, Xu J, Biemesderfer D, Forbush B. Chemical structure. 1 The ion transporters are involved in several brain disorders, including ischemic stroke, epilepsy, traumatic brain injury, and autism. Furosemide (Lasix) is a loop diuretic inhibitor of Na+/2Cl-/K+ (NKCC) cotransporter of which used in the treatment of congestive heart failure and edema. Previous in vivo studies have demonstrated that bumetanide, a selective Na+–K+–2Cl− cotransport inhibitor, attenuates ischemia-evoked cerebral edema. To investigate this possibility, we evaluated the effect of the Na-K-Cl cotransport inhibitor bumetanide on edema formation occurring in response to permanent MCAO. Piechotta K, Garbarini N, England R, Delpire E (2003) Characterization of the interaction of the stress kinase SPAK with the Na +, K +, Cl- cotransporter in the nervous system: evidence for a scaffolding role of the kinase. In particular, activation of the Na-K-Cl cotransporter (NKCC1) has been shown to be involved in cell swelling in several neurological disorders. The human and shark Na-K-Cl cotransporters (NKCCs) are 74% identical in amino acid sequence yet they display marked differences in apparent affinities for the ions and bumetanide. B, Infarct and swelling. The human and shark Na-K-Cl cotransporters (NKCCs) are 74% identical in amino acid sequence yet they display marked differences in apparent affinities for the ions and bumetanide. Plasmalemmal electroneutral NKCC (Na +-K +-Cl − cotransporter) are targets of the loop diuretic drugs furosemide (NKCC2 inhibitor) and bumetanide (BMT; NKCC1 and NKCC2 inhibitor). The human and shark Na–K–Cl cotransporters (NKCC), although 74% identical in amino acid sequence, exhibit marked differences in ion transport and bumetanide binding. This increase was not observed in TNF −/− mice treated with recombinant human TNF (hTNF) for 7 days. Chemical name. Furosemide is a potent and orally active inhibitor of Na+/K+/2Cl- (NKCC) cotransporter, NKCC1 and NKCC2. The Na +-K +-Cl − cotransporter isoform-1 (NKCC-1) appears to play an important role in ischemia-induced neuronal damage to neurons. We have utilized shark–human chimeras of NKCC1 to search for regions that confer the kinetic differences. We therefore examined the effect of ammonia on NKCC activity and its potential role in the swelling of astrocytes. Properties. Suppresses osteoclastic pit formation and Cl - and H + extrusion. The Na-K-Cl cotransporter-1 (NKCC1), in particular, has been shown to play an important role in the mediation of cell swelling/brain edema (for a review, see Ref. Distribution and diversity of Na-K-Cl cotransport proteins: a study with monoclonal antibodies. The Na-K-Cl cotransporter (NKCC) mediates the coupled movement of ions into most animal cells, playing important roles in maintenance of cell volume and in epithelial Cl transport. Under 75 mM [K +] o, astrocytes swelled by 20.2 ± 4.9%. Na + -Cl − cotransporter expression has only been detected in peripheral epithelia ( Russell, 2000 ). Outer medulla from TNF −/− mice exhibited a twofold increase in total NKCC2 protein expression compared with wild-type (WT) mice. Bumetanide is a potent inhibitor of Na +-K +-Cl − cotransporter, but it also blocks other cotransporters, such as K +-Cl − and Na +-Cl −, at greater concentrations (Russell, 2000). Target: NKCC Furosemide (INN/BAN) or frusemide is a loop diuretic used in the treatment of congestive heart failure and edema. We recently found that ammonia, a key etiological factor in ALF, caused the activation of the Na-K-Cl cotransporter-1 (NKCC1) in cultured astrocytes, and that inhibition of such activation led to a reduction in astrocyte swelling, suggesting that NKCC1 activation may be an important factor in the mechanism of brain edema in ALF. 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