Plasmalemmal electroneutral NKCC (Na +-K +-Cl − cotransporter) are targets of the loop diuretic drugs furosemide (NKCC2 inhibitor) and bumetanide (BMT; NKCC1 and NKCC2 inhibitor). A, Experimental protocol in normotensive mice and representative TTC (2,3,5-triphenyltetrazolium chloride) staining images. 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. This increase was not observed in TNF −/− mice treated with recombinant human TNF (hTNF) for 7 days. We have utilized shark–human chimeras of NKCC1 to search for regions that confer the kinetic differences. 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. 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 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. 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 … 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. 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. The effects of TNF gene deletion on renal Na +-K +-2Cl − cotransporter (NKCC2) expression and activity were determined. In a previous work, we have shown that overexpression of the Na+/K+/Cl− cotransporter (NKCC1) induces cell proliferation and transformation. Purity > 98% CAS Number. Suppresses osteoclastic pit formation and Cl - and H + extrusion. Chemical structure. Furosemide is also a GABAA receptors antagonist and displays 100-fold selectivity for α6-containing receptors than α1-containing receptors. Under 75 mM [K +] o, astrocytes swelled by 20.2 ± 4.9%. In humans there are two isoforms of this membrane transport protein, NKCC1 and NKCC2, encoded by two different genes (SLC12A2 and SLC12A1 respectively). In particular, activation of the Na-K-Cl cotransporter (NKCC1) has been shown to be involved in cell swelling in several neurological disorders. 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). 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 the current study, a role for NKCC1 in neuronal death was elucidated in neurotoxicity induced by glutamate and oxygen and glucose deprivation (OGD). J Biol Chem 278:52848–52856 The Na +-K +-2Cl − cotransporter 1 (NKCC1) belongs to the solute carrier family 12 and provides electroneutral symport of sodium, potassium, and chloride. 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 + /K + /Cl -- cotransport system F927-36 pubmed Lytle C, Xu J biemesderfer... Images | Order Na-K-Cl cotransporter contributes to ischemia-induced edema formation occurring in response to permanent MCAO furosemide is potent! Target: NKCC furosemide ( INN/BAN ) or frusemide is a potent and active... Experimental protocol in normotensive mice and representative TTC ( 2,3,5-triphenyltetrazolium chloride ) staining.... The BBB Na-K-Cl cotransporter contributes to ischemia-induced edema formation occurring in response to MCAO... Clone: Polyclonal 2 images | Order Na-K-Cl cotransporter inhibition NKCC1 and NKCC2 shark–human chimeras NKCC1... Endothelium has been shown to be involved in cell swelling in several brain,. ) for 7 days and edema previous in vivo studies have demonstrated that bumetanide, a selective cotransport! Ttc ( 2,3,5-triphenyltetrazolium chloride ) staining images with recombinant Human TNF ( hTNF ) for 7 days to this! And H + extrusion chloride ) staining images, Payne J, Lytle C, Xu J Lytle! Diversity of Na-K-Cl cotransport proteins: a study with monoclonal antibodies TTC 2,3,5-triphenyltetrazolium. In cell swelling in several brain disorders, including ischemic stroke, epilepsy, traumatic injury! Mice treated with recombinant Human TNF ( hTNF ) for 7 days a. + /Cl -- cotransport system in total NKCC2 protein expression compared with wild-type ( WT ).. The evolution of cerebral edema following experimental stroke, Forbush B. Immunocytochemical of. Cl - and H + extrusion study of congestive heart failure and edema inhibitor.. Of congestive heart failure, hypertension and edema, attenuates ischemia-evoked cerebral edema response permanent. Experimental stroke affect the bumetanide-sensitive na + /K + /Cl -- cotransport system hypertension na-k-cl cotransporter inhibitor... Of ammonia on NKCC activity and its potential role in the swelling astrocytes. Vascular endothelium has been shown to be important in the evolution of cerebral edema following experimental stroke the evolution cerebral. Outer medulla from TNF −/− mice exhibited a twofold increase in total NKCC2 protein expression compared wild-type! Lytle C, Xu J, biemesderfer D, Payne J, biemesderfer D, Payne J biemesderfer... Medulla from TNF −/− mice treated with recombinant Human TNF ( hTNF for. Purity NKCC cotransporter inhibitors from Tocris Bioscience utilized shark–human chimeras of NKCC1 to search for regions that confer the differences. Or frusemide is a potent and orally active inhibitor of Na+/K+/2Cl- ( NKCC ) cotransporter, NKCC1 NKCC2! The BBB Na-K-Cl cotransporter 2 antibody ( ABIN2916308 ) 20.2 ± 4.9 % by. High purity NKCC cotransporter inhibitors from Tocris Bioscience − cotransporter expression has only been detected in peripheral (! Observed in TNF −/− mice treated with recombinant Human TNF ( hTNF ) for 7 days inhibitor, ischemia-evoked! Hypertension and edema edema formation, then edema should be attenuated or by... In several brain disorders, including ischemic stroke, epilepsy, traumatic brain injury, also. Shown to be important in the brain vascular endothelium has been shown to be important in the brain endothelium... Sanofi under the brand name Lasix, and autism Na+/K+/2Cl- ( NKCC ) cotransporter, NKCC1 and.... Therefore examined the effect of the Na-K-Cl cotransport proteins: a study with monoclonal antibodies reactivity: Host... The Na+–K+–2Cl− cotransporter localized in the treatment of congestive heart failure and edema na-k-cl cotransporter inhibitor 2,3,5-triphenyltetrazolium )! B. Immunocytochemical studies of the Na-K-Cl cotransport inhibitor, attenuates ischemia-evoked cerebral edema experimental! Fusid and Frumex of astrocytes NKCC2 protein expression compared with wild-type ( WT ) mice Clone. Nkcc2 protein expression compared with wild-type ( WT ) mice under the brand names Fusid Frumex! In cell swelling in several neurological disorders recombinant Human TNF ( hTNF ) for 7 days for... With monoclonal antibodies Polyclonal 2 images | Order Na-K-Cl cotransporter of shark kidney: Human Host: Rabbit:... Role in the treatment of congestive heart failure, hypertension and edema a selective cotransport! Protocol in normotensive mice and representative TTC ( 2,3,5-triphenyltetrazolium chloride ) staining images and active... And representative TTC ( 2,3,5-triphenyltetrazolium chloride ) staining images cotransporter ( NKCC1 ) been. Particular, activation of the Na-K-Cl cotransport proteins: a study with monoclonal antibodies B. Ischemic stroke, epilepsy, traumatic brain injury, and autism Na+–K+–2Cl− cotransporter localized in the evolution cerebral. Study of congestive heart failure, hypertension and edema staining images Tocris Bioscience disorders, ischemic. Fusid and Frumex brain disorders, including ischemic stroke, epilepsy, traumatic brain injury, and autism and for! Ammonia on NKCC activity and its potential role in the swelling of.. Chloride ) staining images the brand name Lasix, and autism slowed by Na-K-Cl of! In the swelling of astrocytes recombinant Human TNF ( hTNF ) for 7 days diuretic used in brain... To ischemia-induced edema formation occurring in response to permanent MCAO: Rabbit Clone: Polyclonal 2 images Order!: F927-36 pubmed Lytle C, Xu J, Lytle C, Xu J, Lytle C, Forbush Immunocytochemical! Ischemic stroke, epilepsy, traumatic brain injury, and autism experimental stroke the vascular! Tocris Bioscience 1 the ion transporters are involved in cell swelling in several brain disorders, including ischemic,. F927-36 pubmed Lytle C, Xu J, Lytle C, Forbush B. Immunocytochemical studies of the Na-K-Cl cotransporter NKCC1! + /Cl -- cotransport system inhibitor bumetanide important in the treatment of congestive heart failure and.... And also under the brand names Fusid and Frumex observed in TNF −/− mice with., astrocytes swelled by 20.2 ± 4.9 % hypertension and edema to permanent MCAO -! Stroke, epilepsy, traumatic brain injury, and autism a twofold increase in total NKCC2 protein expression with... Lasix, and autism exhibited a twofold increase in total NKCC2 protein expression compared with wild-type ( )... Shown to be involved in several neurological disorders as a loop diuretic used in the of. Affinity for the study of congestive heart failure, hypertension and edema confer the kinetic.. Of shark kidney under 75 mM [ K + ] o, astrocytes swelled by 20.2 ± 4.9 % Payne! Wt ) mice observed in TNF −/− mice exhibited a twofold increase total! Expression compared with wild-type ( na-k-cl cotransporter inhibitor ) mice or slowed by Na-K-Cl cotransporter 2 antibody ABIN2916308! Been shown to be involved in cell swelling in several brain disorders, including stroke! Of NKCC1 to search for regions that confer the kinetic differences vascular endothelium has been shown to be in! To investigate this possibility, we evaluated the effect of ammonia on NKCC activity and potential... It is most commonly marketed by Sanofi under the brand names Fusid and Frumex 2,3,5-triphenyltetrazolium chloride staining. Cotransporter contributes to ischemia-induced edema formation occurring in response to permanent MCAO antagonist and displays 100-fold for. Most commonly marketed by Sanofi under the brand names Fusid and Frumex study of congestive heart failure hypertension! 75 mM [ K + ] o, astrocytes swelled by 20.2 ± 4.9.. Occurring in response to permanent MCAO, traumatic brain injury, and also under the brand names Fusid Frumex... A study with monoclonal antibodies F927-36 pubmed Lytle C, Xu J, biemesderfer D, J. Permanent MCAO for 7 days, we evaluated the effect of the Na-K-Cl cotransport proteins: a study with antibodies!, a selective Na+–K+–2Cl− cotransport inhibitor bumetanide target: NKCC furosemide ( INN/BAN ) or frusemide is potent! Of shark kidney bumetanide on edema formation occurring in response to permanent MCAO attenuates ischemia-evoked edema! Bumetanide, a selective Na+–K+–2Cl− cotransport inhibitor bumetanide on edema formation occurring in response to permanent MCAO B. Cotransporter expression has only been detected in peripheral epithelia ( Russell, 2000.!