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https://www.readbyqxmd.com/read/29763692/pharmacological-evidence-that-dapi-inhibits-nhe2-in-fundulus-heteroclitus-acclimated-to-freshwater
#1
Kevin V Brix, Colin J Brauner, Dolph Schluter, Chris M Wood
Ionoregulation in the euryhaline killifish Fundulus heteroclitus has been intensively studied over the last two decades using a variety of techniques. However, there has been limited use of pharmacological inhibitors to identify proteins involved in ion transport for this species. In this study, we used a range of pharmacological inhibitors (EIPA, DAPI, ethoxzolamide, bumetanide, bafilomycin, phenamil, hydrochlorothiazide) to investigate the proteins involved in Na+ transport in freshwater (1 mM Na+ ) acclimated F...
May 12, 2018: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/29739261/exacerbated-brain-edema-in-a-rat-streptozotocin-model-of-hyperglycemic-ischemic-stroke-evidence-for-involvement-of-blood-brain-barrier-na-k-cl-cotransport-and-na-h-exchange
#2
Natalie Y Yuen, Olga V Chechneva, Yi-Je Chen, Yi-Chen Tsai, Logan K Little, James Dang, Daniel J Tancredi, Jacob Conston, Steven E Anderson, Martha E O'Donnell
Cerebral edema is exacerbated in diabetic ischemic stroke through poorly understood mechanisms. We showed previously that blood-brain barrier (BBB) Na-K-Cl cotransport (NKCC) and Na/H exchange (NHE) are major contributors to edema formation in normoglycemic ischemic stroke. Here, we investigated whether hyperglycemia-exacerbated edema involves changes in BBB NKCC and NHE expression and/or activity and whether inhibition of NKCC or NHE effectively reduces edema and injury in a type I diabetic model of hyperglycemic stroke...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29651049/gabaergic-inhibition-in-dual-transmission-cholinergic-and-gabaergic-striatal-interneurons-is-abolished-in-parkinson-disease
#3
N Lozovaya, S Eftekhari, R Cloarec, L A Gouty-Colomer, A Dufour, B Riffault, M Billon-Grand, A Pons-Bennaceur, N Oumar, N Burnashev, Y Ben-Ari, C Hammond
We report that half striatal cholinergic interneurons are dual transmitter cholinergic and GABAergic interneurons (CGINs) expressing ChAT, GAD65, Lhx7, and Lhx6 mRNAs, labeled with GAD and VGAT, generating monosynaptic dual cholinergic/GABAergic currents and an inhibitory pause response. Dopamine deprivation increases CGINs ongoing activity and abolishes GABAergic inhibition including the cortico-striatal pause because of high [Cl- ]i levels. Dopamine deprivation also dramatically increases CGINs dendritic arbors and monosynaptic interconnections probability, suggesting the formation of a dense CGINs network...
April 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29502291/nkcc1-inhibition-attenuates-chronic-cerebral-hypoperfusion-induced-white-matter-lesions-by-enhancing-progenitor-cells-of-oligodendrocyte-proliferation
#4
Ying Yu, Peicai Fu, Zhiyuan Yu, Minjie Xie, Wei Wang, Xiang Luo
Cerebral white matter is vulnerable to ischemic condition. However, no effective treatment to alleviate or restore the myelin damage caused by chronic cerebral hypoperfusion has been found. Na+ -K+ -Cl- cotransporter 1 (NKCC1), a Na+ -K+ -Cl- cotransporter widely expressed in the central nervous system (CNS), involves in regulation of cell swelling, EAA release, cell apoptosis, and proliferation. Nevertheless, the role of NKCC1 in chronic hypoperfusion-induced white matter lesions (WMLs) has not been explored...
March 2018: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29483603/bumetanide-for-autism-more-eye-contact-less-amygdala-activation
#5
Nouchine Hadjikhani, Jakob Åsberg Johnels, Amandine Lassalle, Nicole R Zürcher, Loyse Hippolyte, Christopher Gillberg, Eric Lemonnier, Yehezkel Ben-Ari
We recently showed that constraining eye contact leads to exaggerated increase of amygdala activation in autism. Here, in a proof of concept pilot study, we demonstrate that administration of bumetanide (a NKCC1 chloride importer antagonist that restores GABAergic inhibition) normalizes the level of amygdala activation during constrained eye contact with dynamic emotional face stimuli in autism. In addition, eye-tracking data reveal that bumetanide administration increases the time spent in spontaneous eye gaze during in a free-viewing mode of the same face stimuli...
February 26, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29440005/interaction-between-the-sodium-glucose-linked-transporter-2-inhibitor-dapagliflozin-and-the-loop-diuretic-bumetanide-in-normal-human-subjects
#6
Christopher S Wilcox, Wen Shen, David W Boulton, Bruce R Leslie, Steven C Griffen
BACKGROUND: Dapagliflozin inhibits the sodium-glucose-linked transporter 2 in the renal proximal tubule, thereby promoting glycosuria to reduce hyperglycemia in type 2 diabetes mellitus. Because these patients may require loop diuretics, and sodium-glucose-linked transporter 2 inhibition causes an osmotic diuresis, we evaluated the diuretic interaction between dapagliflozin and bumetanide. METHODS AND RESULTS: Healthy subjects (n=42) receiving a fixed diet with ≈110 mmol·d-1 of Na+ were randomized to bumetanide (1 mg·d-1 ), dapagliflozin (10 mg·d-1 ), or both for 7 days, followed by 7 days of both...
February 10, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29431617/antisecretory-factor-mediated-inhibition-of-cell-volume-dynamics-produces-antitumor-activity-in-glioblastoma
#7
Shirin Ilkhanizadeh, Hanna Sabelström, Yekaterina A Miroshnikova, Aaron Frantz, Wen Zhu, Aurora Idilli, Jon N Lakins, Christin Schmidt, David A Quigley, Trenten Fenster, Edith Yuan, Jacqueline R Trzeciak, Supna Saxena, Olle R Lindberg, Janna K Mouw, Jason A Burdick, Sergey Magnitsky, Mitchel S Berger, Joanna J Phillips, Daniele Arosio, Dandan Sun, Valerie M Weaver, William A Weiss, Anders I Persson
Interstitial fluid pressure (IFP) presents a barrier to drug uptake in solid tumors, including the aggressive primary brain tumor glioblastoma (GBM). It remains unclear how fluid dynamics impacts tumor progression and can be targeted therapeutically. To address this issue, a novel telemetry-based approach was developed to measure changes in IFP during progression of GBM xenografts. Antisecretory factor (AF) is an endogenous protein that displays antisecretory effects in animals and patients. Here, endogenous induction of AF protein or exogenous administration of AF peptide reduced IFP and increased drug uptake in GBM xenografts...
May 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29412704/with-no-lysine-kinase-4-modulates-sodium-potassium-2-chloride-cotransporter-activity-in-vivo
#8
Andrew Scott Terker, Maria Castaneda-Bueno, Mohammed Zubaerul Ferdaus, Ryan J Cornelius, Kayla J Erspamer, Xiao-Tong Su, Lauren N Miller, James A McCormick, Wen-Hui Wang, Gerardo Gamba, Chao-Ling Yang, David H Ellison
With no lysine kinase 4 (WNK4) is essential to activate the thiazide-sensitive NaCl cotransporter (NCC) along the distal convoluted tubule, an effect central to the phenotype of familial hyperkalemic hypertension. Although effects on potassium and sodium channels along the connecting and collecting tubules have also been documented, WNK4 is typically believed to have little role in modulating sodium chloride reabsorption along the thick ascending limb of the loop of Henle. Yet wnk4-/- mice (knockout mice lacking WNK4) do not demonstrate the hypocalciuria typical of pure distal convoluted tubule dysfunction...
February 7, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29403391/pretreatment-with-aqp4-and-nkcc1-inhibitors-concurrently-attenuated-spinal-cord-edema-and-tissue-damage-after-spinal-cord-injury-in-rats
#9
Xiaodong Yan, Juanfang Liu, Xiji Wang, Wenhao Li, Jingyuan Chen, Honghui Sun
Spinal cord injury (SCI) affects more than 2.5 million people worldwide. Spinal cord edema plays critical roles in the pathological progression of SCI. This study aimed to delineate the roles of aquaporin 4 (AQP4) and Na+ -K+ -Cl- cotransporter 1 (NKCC1) in acute phase edema and tissue destruction after SCI and to explore whether inhibiting both AQP4 and NKCC1 could improve SCI-induced spinal edema and damage. Rat SCI model was established by modified Allen's method. Spinal cord water content, cerebrospinal fluid lactose dehydrogenase (LDH) activity, AQP4 and NKCC1 expression, and spinal cord pathology from 30 min to 7 days after SCI were monitored...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29382760/restoring-gabaergic-inhibition-rescues-memory-deficits-in-a-huntington-s-disease-mouse-model
#10
Zahra Dargaei, Jee Yoon Bang, Vivek Mahadevan, C Sahara Khademullah, Simon Bedard, Gustavo Morrone Parfitt, Jun Chul Kim, Melanie A Woodin
Huntington's disease (HD) is classically characterized as a movement disorder, however cognitive impairments precede the motor symptoms by ∼15 y. Based on proteomic and bioinformatic data linking the Huntingtin protein (Htt) and KCC2, which is required for hyperpolarizing GABAergic inhibition, and the important role of inhibition in learning and memory, we hypothesized that aberrant KCC2 function contributes to the hippocampal-associated learning and memory deficits in HD. We discovered that Htt and KCC2 interact in the hippocampi of wild-type and R6/2-HD mice, with a decrease in KCC2 expression in the hippocampus of R6/2 and YAC128 mice...
February 13, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29319897/application-of-a-physiologically-based-pharmacokinetic-model-for-the-prediction-of-bumetanide-plasma-and-brain-concentrations-in-the-neonate
#11
Maria D Donovan, Khaled Abduljalil, John F Cryan, Geraldine B Boylan, Brendan T Griffin
Bumetanide is a loop diuretic that is proposed to possess a beneficial effect on disorders of the central nervous system, including neonatal seizures. Therefore, prediction of unbound bumetanide concentrations in the brain is relevant from a pharmacological prospective. A physiologically-based pharmacokinetic (PBPK) model was developed for the prediction of bumetanide disposition in plasma and brain in adult and paediatric populations. A compound file was built for bumetanide integrating physicochemical data and in vitro data...
March 2018: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/29235092/bumetanide-blocks-the-acquisition-of-conditioned-fear-in-adult-rats
#12
Meng-Chang Ko, Ming-Chung Lee, Tso-Hao Tang, Tamara G Amstislavskaya, Maria A Tikhonova, Yi-Ling Yang, Kwok-Tung Lu
BACKGROUND AND PURPOSE: Administration of bumetanide has anxiolytic effects in rat models of conditioned fear. As a loop diuretic, bumetanide may act as an anxiolytic by modulating GABAergic synaptic transmission through the antagonism of cation-chloride cotransporters (CCCs). Its clinical potential for the treatment of anxiety disorders deserves further investigation. In this study, we evaluated the possible role of the basolateral nucleus of amygdala (BLA) in the anxiolytic effect of bumetanide...
December 12, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29218440/biochemical-properties-of-the-sensitivity-to-gaba-a-ergic-ligands-cl-hco-3-atpase-isolated-from-fish-cyprinus-carpio-olfactory-mucosa-and-brain
#13
Sergey Menzikov
This paper presents a comparative study of the roles of Cl- and HCO3 - in the functioning of the GABAA R-associated Cl- /HCO3 - -ATPase of the plasma membranes of the olfactory sensory neurons (OSNs) and mature brain neurons (MBNs) of fish. The ATPase activity of OSNs and its dephosphorylation were increased twofold by Cl- (15-30 mmol l-1 ), whereas the enzyme from MBNs was not significantly affected by Cl- . By contrast, HCO3 - (15-30 mmol l-1 ) significantly activated the MBN enzyme and its dephosphorylation, but had no effect on the OSN ATPase...
December 7, 2017: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/29209227/the-role-of-na-k-2cl-cotransporter-1-nkcc1-slc12a2-in-dental-epithelium-during-enamel-formation-in-mice
#14
Rozita Jalali, Johannes C Lodder, Behrouz Zandieh-Doulabi, Dimitra Micha, James E Melvin, Marcelo A Catalan, Huibert D Mansvelder, Pamela DenBesten, Antonius Bronckers
Na+ :K+ :2Cl- cotransporters (NKCCs) belong to the SLC12A family of cation-coupled Cl- transporters. We investigated whether enamel-producing mouse ameloblasts express NKCCs. Transcripts for Nkcc1 were identified in the mouse dental epithelium by RT-qPCR and NKCC1 protein was immunolocalized in outer enamel epithelium and in the papillary layer but not the ameloblast layer. In incisors of Nkcc1 -null mice late maturation ameloblasts were disorganized, shorter and the mineral density of the enamel was reduced by 10% compared to wild-type controls...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29204056/effects-of-hemp-seed-soft-capsule-on-colonic-ion-transport-in-rats
#15
Xiao-Fang Lu, Meng-Di Jia, Sheng-Sheng Zhang, Lu-Qing Zhao
AIM: To investigate the effect of Hemp seed soft capsule (HSCC) on colonic ion transport and its related mechanisms in constipation rats. METHODS: Sprague-Dawley male rats were randomly divided into three groups: normal group, constipation group and HSSC group. Rats in the constipation and HSSC groups were administrated loperamide 3 mg/kg per day orally for 12 d to induce the constipation model. Then, the HSSC group was given HSSC 0.126 g/kg per day by gavage for 7 d...
November 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29179179/naringenin-regulates-cftr-activation-and-expression-in-airway-epithelial-cells
#16
Rui Shi, Zi-Ting Xiao, Yi-Jun Zheng, Yi-Lin Zhang, Jia-Wen Xu, Jie-Hong Huang, Wen-Liang Zhou, Pei-Bo Li, Wei-Wei Su
BACKGROUND/AIMS: Sputum symptoms are commonly seen in the elderly. This study aimed to identify an efficacious expectorant treatment stratagem through evaluating the secretion-promoting activation and cystic fibrosis transmembrane conductance regulator (CFTR) expression of the bioactive herbal monomer naringenin. METHODS: Vectorial Cl- transport was determined by measuring short-circuit current (ISC) in rat airway epithelium. cAMP content was measured by ELISA in primary cultured epithelial cells and Calu-3 cells...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29176723/potassium-regulation-in-medaka-oryzias-latipes-larvae-acclimated-to-fresh-water-passive-uptake-and-active-secretion-by-the-skin-cells
#17
Jiun-Lin Horng, Li-Lu Yu, Sian-Tai Liu, Po-Yen Chen, Li-Yih Lin
Molecular mechanisms of Na+ , Cl- , and Ca2+ regulation in ionocytes of fish have been well investigated. However, the regulatory mechanism of K+ in fishes has been largely unknown. In this study, we investigated the mechanism of K+ regulation in medaka larvae acclimated to fresh water. Using a scanning ion-selective electrode technique (SIET) to measure the K+ fluxes at skin cells, significant K+ effluxes were found at ionocytes; in contrast, significant K+ influxes were found at the boundaries between keratinocytes...
November 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29159314/vasoconstriction-triggered-by-hydrogen-sulfide-evidence-for-na-k-2cl-cotransport-and-l-type-ca-2-channel-mediated-pathway
#18
Sergei N Orlov, Svetlana V Gusakova, Liudmila V Smaglii, Svetlana V Koltsova, Svetalana V Sidorenko
Objectives: This study examined the dose-dependent actions of hydrogen sulfide donor sodium hydrosulphide (NaHS) on isometric contractions and ion transport in rat aorta smooth muscle cells (SMC). Methods: Isometric contraction was measured in ring aortas segments from male Wistar rats. Activity of Na+ /K+ -pump and Na+ ,K+ ,2Cl- cotransport was measured in cultured endothelial and smooth muscle cells from the rat aorta as ouabain-sensitive and ouabain-resistant, bumetanide-sensitive components of the86 Rb influx, respectively...
December 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/29146941/developmental-excitatory-to-inhibitory-gaba-polarity-switch-is-disrupted-in-22q11-2-deletion-syndrome-a-potential-target-for-clinical-therapeutics
#19
Hayder Amin, Federica Marinaro, Davide De Pietri Tonelli, Luca Berdondini
Individuals with 22q11.2 microdeletion syndrome (22q11.2 DS) show cognitive and behavioral dysfunctions, developmental delays in childhood and risk of developing schizophrenia and autism. Despite extensive previous studies in adult animal models, a possible embryonic root of this syndrome has not been determined. Here, in neurons from a 22q11.2 DS mouse model (Lgdel+/- ), we found embryonic-premature alterations in the neuronal chloride cotransporters indicated by dysregulated NKCC1 and KCC2 protein expression levels...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29029515/discovery-of-nkcc1-as-a-potential-therapeutic-target-to-inhibit-hepatocellular-carcinoma-cell-growth-and-metastasis
#20
Yaya Zhou, Wei Sun, Ning Chen, Chen Xu, Xinxin Wang, Kun Dong, Binxue Zhang, Jian Zhang, Ning Hao, Aihua Sun, Handong Wei, Fuchu He, Ying Jiang
Metastasis is the essential cause for the high mortality of hepatocellular carcinoma (HCC). In order to investigate the mechanism of metastasis, and to discover therapeutic targets for HCC, the quantitative proteomic technique was applied to characterize the plasma membrane proteins of two HCC cell lines with low (MHCC97L) or high (MHCC97H) metastatic potentials. One of the plasma membrane proteins, sodium-potassium-chloride cotransporter 1 (NKCC1), was upregulated in MHCC97H cell line. Immunohistochemistry result in HCC patients showed that NKCC1 expression was associated with poor differentiation and microvascular invasion...
September 12, 2017: Oncotarget
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