Thick ascending limb claudins are altered to increase calciuria and magnesiuria in metabolic acidosis

2021 ◽  
Author(s):  
Il Hwan Oh ◽  
Chor Ho Jo ◽  
Sua Kim ◽  
Sungsin Jo ◽  
Sungjin Chung ◽  
...  
Keyword(s):  
Metabolic Acidosis ◽  
Immunofluorescence Microscopy ◽  
Urinary Calcium ◽  
Receptor Protein ◽  
Thick Ascending Limb ◽  
Sprague Dawley ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing ◽  
Sprague Dawley Rats ◽  
Calcium And Magnesium

Urinary calcium and magnesium wasting is a characteristic feature of metabolic acidosis, and this study focused on the role of the thick ascending limb of Henle's loop in metabolic acidosis-induced hypercalciuria and hypermagnesiuria because thick ascending limb is an important site of paracellular calcium and magnesium reabsorption. Male Sprague-Dawley rats were used to determine the effects of acid loading (by adding NH4Cl 7.2 mmol/220 g BW/d to food slurry for 7 days) on renal expression of claudins and then to evaluate whether the results were reversed by antagonizing calcium-sensing receptor (using NPS-2143). At the end of each animal experiment, the kidneys were harvested for immunoblotting, immunofluorescence microscopy and qPCR analysis of claudins and the calcium-sensing receptor. As expected, NH4Cl loading lowered urinary pH and increased excretion of urinary calcium and magnesium. In NH4Cl-loaded rats, renal protein and mRNA expression of claudin-16, and claudin-19 decreased compared with controls. However, claudin-14 protein and mRNA increased in NH4Cl-loaded rats. Consistently, the calcium-sensing receptor protein and mRNA were upregulated in NH4Cl-loaded rats. All these changes were reversed by NPS-2143 coadministration and were confirmed using immunofluorescence microscopy. Hypercalciuria and hypermagnesiuria in NH4Cl-loaded rats were significantly ameliorated by NPS-2143 coadministration as well. We conclude that in metabolic acidosis, claudin-16 and claudin-19 in the thick ascending limb are downregulated to produce hypercalciuria and hypermagnesiuria via the calcium-sensing receptor.

Type-5 Bartter syndrome presenting with metabolic seizure in adulthood

2021 ◽  
Vol 14 (2) ◽  
pp. e235349
Author(s):  
Aqeel Hussain ◽  
Mahendra Atlani ◽  
Abhishek Goyal ◽  
Alkesh Kumar Khurana
Keyword(s):  
Age Of Onset ◽  
Bartter Syndrome ◽  
Electrolyte Imbalance ◽  
Thick Ascending Limb ◽  
Calcium Sensing Receptor ◽  
Inherited Disorders ◽  
Calcium Sensing ◽  
Aged Woman ◽  
Middle Aged Woman ◽  
Renal Tubular

Bartter syndrome is a very rare and heterogeneous disease with variable age of onset and symptom severity. Genotypically they have inherited disorders of the thick ascending limb in the renal tubular system, which manifest phenotypically as electrolyte imbalance due to loss of sodium, chloride and potassium. Gain of function mutations in the calcium-sensing receptor has been described in some patients with Bartter’s syndrome (type-5 Bartter syndrome or autosomal dominant hypocalcaemia with Bartter syndrome) associated with hypocalcaemia and hypercalciuria differentiating it from Gitelman syndrome. This phenotype has been reported to present in adulthood with metabolic abnormalities. We present a case of a middle-aged woman who presented with metabolic seizures and on evaluation was found to have profound electrolyte abnormalities which were corrected with supplements and led to the resolution of symptoms.

scholarly journals Regulation of the Putative TRPV1t Salt Taste Receptor by Phosphatidylinositol 4, 5-Bisphosphate

2010 ◽  
Vol 103 (3) ◽  
pp. 1337-1349 ◽  
Author(s):  
Vijay Lyall ◽  
Tam-Hao T. Phan ◽  
ZuoJun Ren ◽  
Shobha Mummalaneni ◽  
Pamela Melone ◽  
...  
Keyword(s):  
Monosodium Glutamate ◽  
Taste Receptor ◽  
Receptor Protein ◽  
Chorda Tympani ◽  
Sprague Dawley ◽  
Salt Taste ◽  
Sprague Dawley Rats ◽  
Enhanced Ct ◽  
Biphasic Effect ◽  
Phosphatidylinositol 4

Regulation of the putative amiloride and benzamil (Bz)-insensitive TRPV1t salt taste receptor by phosphatidylinositol 4,5-bisphosphate (PIP2) was studied by monitoring chorda tympani (CT) taste nerve responses to 0.1 M NaCl solutions containing Bz (5 × 10−6 M; a specific ENaC blocker) and resiniferatoxin (RTX; 0–10 × 10−6 M; a specific TRPV1 agonist) in Sprague-Dawley rats and in wildtype (WT) and TRPV1 knockout (KO) mice. In rats and WT mice, RTX elicited a biphasic effect on the NaCl + Bz CT response, increasing the CT response between 0.25 × 10−6 and 1 × 10−6 M. At concentrations >1 × 10−6 M, RTX inhibited the CT response. An increase in PIP2 by topical lingual application of U73122 (a phospholipase C blocker) or diC8-PIP2 (a short chain synthetic PIP2) inhibited the control NaCl + Bz CT response and decreased its sensitivity to RTX. A decrease in PIP2 by topical lingual application of phenylarsine oxide (a phosphoinositide 4 kinase blocker) enhanced the control NaCl + Bz CT response, increased its sensitivity to RTX stimulation, and inhibited the desensitization of the CT response at RTX concentrations >1 × 10−6 M. The ENaC-dependent NaCl CT responses were not altered by changes in PIP2. An increase in PIP2 enhanced CT responses to sweet (0.3 M sucrose) and bitter (0.01 M quinine) stimuli. RTX produced the same increase in the Bz-insensitive Na+response when present in salt solutions containing 0.1 M NaCl + Bz, 0.1 M monosodium glutamate + Bz, 0.1 M NaCl + Bz + 0.005 M SC45647, or 0.1 M NaCl + Bz + 0.01 M quinine. No effect of RTX was observed on CT responses in WT mice and rats in the presence of the TRPV1 blocker N-(3-methoxyphenyl)-4-chlorocinnamide (1 × 10−6 M) or in TRPV1 KO mice. We conclude that PIP2 is a common intracellular effector for sweet, bitter, umami, and TRPV1t-dependent salt taste, although in the last case, PIP2 seems to directly regulate the taste receptor protein itself, i.e., the TRPV1 ion channel or its taste receptor variant, TRPV1t.

Role of arginine vasopressin in medullary thick ascending limb on maximal urinary concentration

1986 ◽  
Vol 251 (2) ◽  
pp. F266-F270 ◽  
Author(s):  
J. K. Kim ◽  
S. N. Summer ◽  
A. E. Erickson ◽  
R. W. Schrier
Keyword(s):  
Adenylate Cyclase ◽  
Arginine Vasopressin ◽  
Urinary Concentration ◽  
Thick Ascending Limb ◽  
Sprague Dawley ◽  
Urinary Osmolality ◽  
Medullary Thick Ascending Limb ◽  
Sprague Dawley Rats ◽  
Collecting Tubules

Two groups of Sprague-Dawley rats, Harlan (H) and Charles River (CR), were discovered in that the medullary thick ascending limb (MAL) had a profoundly different adenylate cyclase response to arginine vasopressin (AVP). Using these two groups of rats, we studied the correlation between AVP action on the MAL and maximal urinary concentration. AVP (10(-6) M) significantly stimulated adenylate cyclase in MAL of H rats (7.4 +/- 0.9 to 43.8 +/- 4.6 fmol cAMP formed X 30 min-1 X mm-1, P less than 0.001) but not in CR rats (10.3 +/- 1.4 to 12.7 +/- 2.0 fmol cAMP formed X 30 min-1 X mm-1, NS). In contrast, AVP significantly stimulated adenylate cyclase of cortical, outer and inner medullary collecting tubules from both H and CR rats. Glucagon (10(-6) M) significantly stimulated adenylate cyclase of MAL from both H and CR rats. After 48 h of fluid deprivation, urinary osmolality was significantly higher (P less than 0.001) in the H (4,504 +/- 399 mosmol/kg H2O, n = 14) than CR (2,840 +/- 176 mosmol/kg H2O, n = rats. This observation was not attributable to differences in creatinine clearance (CR, 1.30 +/- 0.24; H, 1.24 +/- 0.03 ml/min, NS, n = 4) or plasma AVP (CR, 12.75 +/- 1.44; H, 12.38 +/- 1.17 pg/ml, NS, n = 6) levels. These results therefore suggest that the action of AVP on the MAL, in addition to the effect on collecting tubules, is involved in maximal urinary concentration in rats.

scholarly journals Hipocalcemia Crónica por Anticorpos Anti-Recetor do Cálcio

2014 ◽  
Vol 27 (3) ◽  
pp. 399
Author(s):  
Pedro Marques ◽  
Rita Santos ◽  
Branca Cavaco ◽  
Valeriano Leite
Keyword(s):  
Parathyroid Hormone ◽  
Genetic Disorder ◽  
Neck Surgery ◽  
Urinary Calcium ◽  
Clinical Report ◽  
Calcium Sensing Receptor ◽  
Casr Gene ◽  
Calcium Sensing ◽  
Calcium Phosphorus ◽  
Receptor Antibodies

<strong>Introduction:</strong> Hypoparathyroidism is an entity associated with hypocalcemia, more frequently a consequence of neck surgery. An autoimmune etiology is rare and its diagnosis difficult to establish.<br /><strong>Clinical report:</strong> 52 year-old woman, with irrelevant past medical history and no significant familial conditions, referred because of hypocalcemia and basal ganglia calcifications, detected in the course of investigation of myalgias. Besides hypocalcemia (4.6 mg/ dL), hyperphosphatemia (8.7 mg/dL), undetectable parathyroid hormone and low urinary calcium, phosphorus and magnesium were present. Molecular analysis of CaSR gene excluded germinal mutations. Anti-calcium sensing receptor antibodies (anti-CaSR) were present. The patient is asymptomatic and normocalcemic under treatment with calcium and vitamin D.<br /><strong>Discussion:</strong> Although rare, hypocalcemia due to anti-CaSR hypoparathyroidism must be considered in the absence of previous neck surgery, hypocalcemic drugs, familial history or phenotype suggesting a genetic disorder. Low or undetectable parathyroid hormone excludes pseudohypoparathyroidism and anti-CaSR positivity establishes the diagnosis.<br /><strong>Keywords:</strong> Hypocalcemia; Hypoparathyroidism; Autoantibodies; Receptors, Calcium-Sensing.

scholarly journals Relevance of a Hypersaline Sodium-Rich Naturally Sparkling Mineral Water to the Protection against Metabolic Syndrome Induction in Fructose-Fed Sprague-Dawley Rats: A Biochemical, Metabolic, and Redox Approach

2014 ◽  
Vol 2014 ◽  
pp. 1-17 ◽  
Author(s):  
Cidália Dionísio Pereira ◽  
Milton Severo ◽  
João Ricardo Araújo ◽  
João Tiago Guimarães ◽  
Diogo Pestana ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Metabolic Syndrome ◽  
Mineral Water ◽  
Tap Water ◽  
Magnesium Content ◽  
Atherosclerotic Cardiovascular Disease ◽  
Sprague Dawley ◽  
The Metabolic Syndrome ◽  
Sprague Dawley Rats ◽  
Calcium And Magnesium

The Metabolic Syndrome increases the risk for atherosclerotic cardiovascular disease and type 2 Diabetes Mellitus. Increased fructose consumption and/or mineral deficiency have been associated with Metabolic Syndrome development. This study aimed to investigate the effects of 8 weeks consumption of a hypersaline sodium-rich naturally sparkling mineral water on 10% fructose-fed Sprague-Dawley rats (Metabolic Syndrome animal model). The ingestion of the mineral water (rich in sodium bicarbonate and with higher potassium, calcium, and magnesium content than the tap water used as control) reduced/prevented not only the fructose-induced increase of heart rate, plasma triacylglycerols, insulin and leptin levels, hepatic catalase activity, and organ weight to body weight ratios (for liver and both kidneys) but also the decrease of hepatic glutathione peroxidase activity and oxidized glutathione content. This mineral-rich water seems to have potential to prevent Metabolic Syndrome induction by fructose. We hypothesize that its regular intake in the context of modern diets, which have a general acidic character interfering with mineral homeostasis and are poor in micronutrients, namely potassium, calcium, and magnesium, could add surplus value and attenuate imbalances, thus contributing to metabolic and redox health and, consequently, decreasing the risk for atherosclerotic cardiovascular disease.

Localization and quantitative expression of the calcium-sensing receptor protein in human oocytes

2006 ◽  
Vol 85 ◽  
pp. 1240-1247 ◽  
Author(s):  
M ELENADELLAQUILA ◽  
T DESANTIS ◽  
Y CHO ◽  
S RESHKIN ◽  
A CAROLI ◽  
...  
Keyword(s):  
Receptor Protein ◽  
Calcium Sensing Receptor ◽  
Human Oocytes ◽  
Quantitative Expression ◽  
Calcium Sensing

Immunolocalization of ectonucleotidases along the rat nephron

2006 ◽  
Vol 290 (2) ◽  
pp. F550-F560 ◽  
Author(s):  
Renu M. Vekaria ◽  
David G. Shirley ◽  
Jean Sévigny ◽  
Robert J. Unwin
Keyword(s):  
Collecting Duct ◽  
Distal Tubule ◽  
Extracellular Nucleotides ◽  
Thick Ascending Limb ◽  
Sprague Dawley ◽  
Low Level ◽  
Amplification Method ◽  
Sprague Dawley Rats ◽  
Collecting Ducts ◽  
Calbindin D

Evidence is accumulating that extracellular nucleotides act as autocrine/paracrine agents in most tissues, including the kidneys. Several families of surface-located enzymes, collectively known as ectonucleotidases, can degrade nucleotides. Using immunohistochemistry, we have examined the segmental distribution of five ectonucleotidases along the rat nephron. Perfusion-fixed kidneys were obtained from anesthetized male Sprague-Dawley rats. Cryostat sections of cortical and medullary regions were incubated with antibodies specific to the following enzymes: ectonucleoside triphosphate diphosphohydrolase (NTPDase) 1, NTPDase2, NTPDase3, ectonucleotide pyrophosphatase phosphodiesterase 3 (NPP3), and ecto-5′-nucleotidase. Sections were then costained with Phaseolus vulgaris erythroagglutinin (for identification of proximal tubules) and antibodies against Tamm-Horsfall protein (for identification of thick ascending limb), calbindin-D28k (for identification of distal tubule), and aquaporin-2 (for identification of collecting duct). The tyramide signal amplification method was used when the ectonucleotidase and marker antibody were raised in the same species. The glomerulus expressed NTPDase1 and NPP3. The proximal tubule showed prominent expression of NPP3 and ecto-5′-nucleotidase in most, but not all, segments. NTPDase2 and NTPDase3, but not NPP3 or ecto-5′-nucleotidase, were expressed in the thick ascending limb and distal tubule. NTPDase3, with some low-level expression of ecto-5′-nucleotidase, was also found in cortical and outer medullary collecting ducts. Inner medullary collecting ducts displayed low-level staining for NTPDase1, NTPDase2, NTPDase3, and ecto-5′-nucleotidase. We conclude that these ectonucleotidases are differentially expressed along the nephron and may play a key role in activation of purinoceptors by nucleotides and nucleosides.

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