- Dissociation of sodium-chloride cotransporter expression and blood pressure during chronic high dietary potassium supplementation. [Journal Article]JCI Insight. 2023 Jan 31 [Online ahead of print]JI
- Dietary potassium (K+) supplementation is associated with a blood pressure (BP) lowering effect, but not all studies agree. Here we examined the effects of short and long-term K+ supplementation on BP in mice, whether differences depend on the accompanying anion or the sodium (Na+) intake and molecular alterations in the kidney that may underlie BP changes. Relative to the control diet, BP was hi…
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- TASK inhibition by mild acidosis increases Ca2+ oscillations to mediate pH sensing in rat carotid body chemoreceptor cells. [Journal Article]Am J Physiol Lung Cell Mol Physiol. 2023 Jan 24 [Online ahead of print]AJ
- Severe levels of acidosis (pH<6.8) have been shown to cause a sustained rise in cytosolic Ca2+ concentration in carotid body Type 1 (glomus) cells. To understand how physiologically relevant levels of acidosis regulate Ca2+ signaling in glomus cells, we studied the effects of small changes in extracellular pH (pHo) on the kinetics of Ca2+ oscillations. A decrease in pHo from 7.4 to 7.3 (designate…
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- Effect of Esomeprazole Treatment on Extracellular Tumor pH in a Preclinical Model of Prostate Cancer by MRI-CEST Tumor pH Imaging. [Journal Article]
- Novel anticancer treatments target the pH regulating system that plays a major role in tumor progression by creating an acidic microenvironment, although few studies have addressed their effect on tumor acidosis. In this study, we investigated in vivo several proton pump inhibitors (PPIs) targeting NHE-1 (Amiloride and Cariporide) and V-ATPase (Esomeprazole and Lansoprazole) proton transporters i…
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- Inhibition of Voltage-Gated Na+ Currents Exerted by KB-R7943 (2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea), an Inhibitor of Na+-Ca2+ Exchanging Process. [Journal Article]
- KB-R7943, an isothiourea derivative, has been recognized as an inhibitor in the reverse mode of the Na+-Ca2+ exchanging process. This compound was demonstrated to prevent intracellular Na+-dependent Ca2+ uptake in intact cells; however, it is much less effective at preventing extracellular Na+-dependent Ca2+ efflux. Therefore, whether or how this compound may produce any perturbations on other ty…
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- Extracellular intersubunit interactions modulate epithelial Na+ channel gating. [Journal Article]J Biol Chem. 2023 Jan 14 [Online ahead of print]JB
- Epithelial Na+ channels (ENaCs) and related channels have large extracellular domains where specific factors interact and induce conformational changes, leading to altered channel activity. However, extracellular structural transitions associated with changes in ENaC activity are not well defined. Using crosslinking and two-electrode voltage clamp in Xenopus oocytes, we identified several pairs o…
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- Tocotrienols: Exciting Biological and Pharmacological Properties of Tocotrienols and other Naturally Occurring Compounds, Part I. [Journal Article]
- Inflammation has been implicated in cardiovascular disease and tocotrienols are potent hypocholesterolemic agents that reduce β-hydroxy-β-methyl-glutaryl coenzyme A reductase activity, which is degraded via the ubiquitin-proteasome pathway. Impact of various tocotrienols (α-, γ-, or δ-tocotrienol) treatments inhibit the chymotrypsin-like activity of 20S rabbit muscle proteasome (>50%) in RAW 264.…
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- A novel mechanism for T1R-independent taste responses to concentrated sugars. [Journal Article]J Neurosci. 2023 Jan 06 [Online ahead of print]JN
- Recent findings from our laboratory demonstrated that the rostral nucleus of solitary tract (rNST) retains some responsiveness to sugars in double-knockout mice lacking either the T1R1+T1R3 (KO1+3) or T1R2+T1R3 (KO2+3) taste receptor heterodimers. Here, we extended these findings in the parabrachial nucleus (PBN) of male and female KO1+3 mice using warm stimuli to optimize sugar responses and emp…
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- An electrolyte flip flop - a patient with chronic hyperkalemic acidosis presenting with severe hypokalemic alkalosis. [Case Reports]
- A 76-year-old man was evaluated in our emergency department (ED) for right toe swelling and pain. His initial ED workup revealed volume overload, uncontrolled hypertension, slow atrial fibrillation, refractory hypokalemia, mixed metabolic alkalosis and respiratory acidosis, with a normal plasma pH, and hypernatremia. His medical chart revealed long standing hyperkalemia and metabolic acidosis, re…
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- Diuretic and Natriuretic Effects of Hesperidin, a Flavanone Glycoside, in Female and Male Hypertensive Rats. [Journal Article]
- Hesperidin (HSP) is a major flavanone glycoside in citrus fruits, including sweet oranges and lemons. It demonstrates numerous pharmacological activities, such as antihypertensive effects and cardiac and kidney tissue protection. However, its effect on modulating renal function has yet to be properly explored. Female and male Wistar spontaneously hypertensive rats (SHR) were used to test the effe…
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- Liddle syndrome. [Journal Article]Vnitr Lek. 2022 Winter; 68(E-8):8-11.VL
- Liddle syndrome is an inherited form of arterial hypertension with autosomal dominant pattern of inheritance. It is caused by activating mutation of genes coding of the epithelial sodium channel in distal nephron. Mutation leads to excessive reabsorbtion of sodium ions and volume expansion resulting in arterial hypertension. Antoher typical laboratory findings are hypokalaemia, low levels of seru…
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- Tocotrienols: Exciting Biological and Pharmacological Properties of Tocotrienols and Naturally Occurring Compounds, Part II. [Journal Article]
- δ-Tocotrienol plus AHA Step-1 diet in hypercholesterolemic subjects caused reductions in lipid parameters (14% to 18%) with 250 mg/d dose, and 500 mg/d resulted induction in these parameters. Although, α-tocopherol is the most bioavailable form of vitamin E. There are few reports on bioavailability of tocotrienols in humans. Pharmacokinetics and bioavailability of δ-tocotrienol was quantified on …
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- Identification of a pharmacological approach to reduce ACE2 expression and development of an in vitro COVID-19 viral entry model. [Journal Article]
- Because of rapid emergence and circulation of the SARS-CoV-2 variants, especially Omicron which shows increased transmissibility and resistant to antibodies, there is an urgent need to develop novel therapeutic drugs to treat COVID-19. In this study we developed an in vitro cellular model to explore the regulation of ACE2 expression and its correlation with ACE2-mediated viral entry. We examined …
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- Targeting Na-H exchanger 1 overcomes nuclear factor kappa B-mediated tumor resistance to radiotherapy. [Journal Article]
- Intrinsic or acquired radioresistance often limits the efficacy of radiation therapy (RT), thereby leading to local control failure. Cancerous cells have abnormal pH dynamics due to high metabolic demands, but it is unclear how pH dynamics contribute to radioresistance. In this study, we investigated the role of Na-H exchange 1 (NHE1), the major intracellular pH (pHi) regulator, in RT response. W…
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- Lipid Profiles of Urinary Extracellular Vesicles Released during the Inactive and Active Phases of Aged Male Mice with Spontaneous Hypertension. [Journal Article]
- Hypertension remains a major problem, especially in the elderly, as it increases the risk for cardiovascular, coronary artery, cerebrovascular, and kidney diseases. Extracellular vesicles (EVs) play a role in the aging process and contribute to pathophysiology. Our goal was to examine differences in lipid profiles of urinary EVs (uEVs) collected during the inactive and active phases of aged mice …
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- Characterization in Potent Modulation on Voltage-Gated Na+ Current Exerted by Deltamethrin, a Pyrethroid Insecticide. [Journal Article]
- Deltamethrin (DLT) is a type-II pyrethroid ester insecticide used in agricultural and domestic applications as well as in public health. However, transmembrane ionic channels perturbed by this compound remain largely unclear, although the agent is thought to alter the gating characteristics of voltage-gated Na+ (NaV) channel current. In this study, we reappraised whether and how it and other rela…
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- A case report of a young boy with low renin and high aldosterone levels induced by Liddle syndrome who was previously misdiagnosed with primary aldosteronism. [Case Reports]J Pediatr Endocrinol Metab. 2022 Dec 06 [Online ahead of print]JP
- CONCLUSIONS: Adolescent hypertension may be secondary to underlying medical conditions affecting the heart, kidneys, or endocrine system or primary with no known underlying disease process. Although in an adolescent with hypertension, hyperaldosteronism, and low plasma renin activity, the initial diagnosis suggested primary hyperaldosteronism, the failure of aldosterone receptor antagonist's therapy led to the diagnosis of Liddle syndrome. Increased aldosterone levels should always be evaluated with caution before a definitive diagnosis to prevent misdiagnosis. Genetic testing is the gold standard for the diagnosis of Liddle syndrome. Early diagnosis and early precise treatment can restore normal blood pressure and prevent severe sequelae of chronic hypertension in patients.
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- Effect of kokumi taste-active γ-glutamyl peptides on amiloride-sensitive epithelial Na+ channels in rat fungiform taste cells. [Journal Article]
- Kokumi taste-active compounds enhance salty taste perception. In animal models, sodium (salt) detection is mediated by the amiloride-sensitive epithelial sodium channel, ENaC. This ion channel works as a sodium receptor in the so-called sodium-taste cells. It is not known whether kokumi taste substances are able to affect the activity of functional ENaCs in these cells. Here, we use the patch-cla…
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- Malate reduced blood pressure and exerted differential effects on renal hemodynamics; role of the nitric oxide system and renal epithelial sodium channels (ENaC). [Journal Article]
- Malate regulates blood pressure via nitric oxide production in salt-sensitive rats, a genetic model of hypertension. This study investigated the possible contributions of malate to blood pressure regulation and renal haemodynamics in normotensive rats. Malate (0.1, 0.3 and 1 μg/kg, iv) was injected into rats or L-nitro-arginine methyl ester (L-NAME)-treated rats and mean arterial blood pressure (…
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- Molecular logic of salt taste reception in special reference to transmembrane channel-like 4 (TMC4). [Review]
- The taste is biologically of intrinsic importance. It almost momentarily perceives environmental stimuli for better survival. In the early 2000s, research into taste reception was greatly developed with discovery of the receptors. However, the mechanism of salt taste reception is not fully elucidated yet and many questions still remain. At present, next-generation sequencing and genome-editing te…
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- Targeting Multiple Homeostasis-Maintaining Systems by Ionophore Nigericin Is a Novel Approach for Senolysis. [Journal Article]
- Within the present study we proposed a novel approach for senolysis based on the simultaneous disturbance of the several homeostasis-maintaining systems in senescent cells including intracellular ionic balance, energy production and intracellular utilization of damaged products. Of note, we could not induce senolysis by applying ouabain, amiloride, valinomycin or NH4Cl-compounds that modify each …
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- Ex Vivo Pulmonary Oedema after In Vivo Blast-Induced Rat Lung Injury: Time Dependency, Blast Intensity and Beta-2 Adrenergic Receptor Role. [Journal Article]
- Objective: Current treatments for blast-induced lung injury are limited to supportive procedures including mechanical ventilation. The study aimed to investigate the role of post-trauma-induced oedema generation in the function of time and trauma intensity and the probable role of beta 2-adrenergic receptors (β2-ARs) agonists on pulmonary oedema. The study is conducted using an ex vivo model afte…
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- Acid-sensitive ion channel 1a regulates TNF-α expression in LPS-induced acute lung injury via ERS-CHOP-C/EBPα signaling pathway. [Journal Article]Mol Immunol. 2023 Jan; 153:25-35.MI
- CONCLUSIONS: ASIC1a regulates the expression of TNF-α in LPS-induced acute lung injury via ERS-CHOP-C/EBPα signaling pathway.
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- Reduced sodium absorption in the colon under serotonin is a potential factor aggravating secretory diarrhea. [Journal Article]Adv Clin Exp Med. 2022 Nov 14 [Online ahead of print]AC
- CONCLUSIONS: Serotonin reduces both stationary and stimulated sodium ion absorption, thus playing an important role in the pathophysiology of secretory diarrhea. The described phenomenon depends on serotonin's action on 5-HT4 receptors.
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- Depletion of Na+/H+ Exchanger Isoform 1 Increases the Host Cell Resistance to Trypanosoma cruzi Invasion. [Journal Article]
- Na+/H+ exchanger isoform 1 (NHE1), a member of a large family of integral membrane proteins, plays a role in regulating the cortical actin cytoskeleton. Trypanosoma cruzi, the agent of Chagas disease, depends on F-actin rearrangement and lysosome mobilization to invade host cells. To determine the involvement of NHE1 in T. cruzi metacyclic trypomastigote (MT) internalization, the effect of treatm…
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- Development of ASIC1a ligand-gated ion channel drug screening assays across multiple automated patch clamp platforms. [Journal Article]
- Human acid-sensing ion channels (ASIC) are ligand-gated ionotropic receptors expressed widely in peripheral tissues as well as sensory and central neurons and implicated in detection of inflammation, tissue injury, and hypoxia-induced acidosis. This makes ASIC channels promising targets for drug discovery in oncology, pain and ischemia, and several modulators have progressed into clinical trials.…
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- Evaluating the clinical and mechanistic effects of eplerenone and amiloride monotherapy, and combination therapy with cinacalcet, in primary hyperparathyroidism: A placebo-controlled randomized trial. [Journal Article]Clin Endocrinol (Oxf). 2022 Oct 31 [Online ahead of print]CE
- CONCLUSIONS: Although maximally tolerated therapy with eplerenone and amiloride induced expected changes in renin, aldosterone and blood pressure, there were no meaningful changes in PTH or serum calcium levels in P-HPT patients. These results suggest that inhibition of aldosterone action does not have a clinically meaningful role in medical therapy for P-HPT.
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- Severe hyponatremia due to trimethoprim-sulfamethoxazole-induced SIADH. [Case Reports]
- Hyponatremia, a serum sodium level of <135 mEq/L, is the most common electrolyte abnormality occurring in 5%-35% of hospitalized patients. It is a predictor of increased morbidity and mortality. Diuretics, psychotropic, and antiepileptic drugs are commonly implicated in drug-induced hyponatremia. Trimethoprim-sulfamethoxazole and spironolactone are two commonly prescribed drugs; unfortunately, mo…
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- Blood-Brain Barrier Solute Carrier Transporters and Motor Neuron Disease. [Review]
- Defective solute carrier (SLC) transporters are responsible for neurotransmitter dysregulation, resulting in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). We provided the role and kinetic parameters of transporters such as ASCTs, Taut, LAT1, CAT1, MCTs, OCTNs, CHT, and CTL1, which are mainly responsible for the transport of essential nutrients, acidic, and basic drugs in…
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- Polycystin-2 (TRPP2) regulates primary cilium length in LLC-PK1 renal epithelial cells. [Journal Article]
- Polycystin-2 (PC2, TRPP2) is a Ca2+ permeable nonselective cation channel whose dysfunction generates autosomal dominant polycystic kidney disease (ADPKD). PC2 is present in different cell locations, including the primary cilium of renal epithelial cells. However, little is known as to whether PC2 contributes to the primary cilium structure. Here, we explored the effect(s) of external Ca2+, PC2 c…
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- Changes of the biophysical properties of voltage-gated Na+ currents during maturation of the sodium-taste cells in rat fungiform papillae. [Journal Article]J Physiol. 2022 12; 600(23):5119-5144.JP
- Taste cells are a heterogeneous population of sensory receptors that undergo continuous turnover. Different chemo-sensitive cell lines rely on action potentials to release the neurotransmitter onto nerve endings. The electrical excitability is due to the presence of a tetrodotoxin-sensitive, voltage-gated sodium current (INa) similar to that found in neurons. Since the biophysical properties of n…
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