scholarly journals Participation of mercuric conjugates of cysteine, homocysteine, and N-acetylcysteine in mechanisms involved in the renal tubular uptake of inorganic mercury.

1998 ◽  
Vol 9 (4) ◽  
pp. 551-561
Author(s):  
R K Zalups ◽  
D W Barfuss
Keyword(s):  
Basolateral Membrane ◽  
Inorganic Mercury ◽  
Fecal Excretion ◽  
Outer Medulla ◽  
Renal Uptake ◽  
Luminal Membrane ◽  
Outer Stripe ◽  
Mercuric Ions ◽  
Renal Tubular ◽  
The One

Mechanisms involved in the renal uptake of inorganic mercury were studied in rats administered a nontoxic 0.5 mumol/kg intravenous dose of inorganic mercury with or without 2.0 mumol/kg cysteine, homocysteine, or N-acetylcysteine. The renal disposition of mercury was studied 1 h after treatment in normal rats and rats that had undergone bilateral ureteral ligation. In addition, the disposition of mercury (including the urinary and fecal excretion of mercury) was evaluated 24 h after treatment. In normal rats, coadministering inorganic mercury plus cysteine or homocysteine caused a significant increase in the renal uptake of mercury 1 h after treatment. The enhanced renal uptake of mercury was due to increased uptake of mercury in the renal outer stripe of the outer medulla and/or renal cortex. Ureteral ligation caused reductions in the renal uptake of mercury in all groups except for the one treated with inorganic mercury plus N-acetylcysteine. Thus, it appears that virtually all of the mercury taken up by the kidneys of the normal rats treated with inorganic mercury plus N-acetylcysteine occurred at the basolateral membrane. Urinary excretory data also support this notion, in that the rate of excretion of inorganic mercury was greatest in the rats treated with inorganic mercury plus N-acetylcysteine. Our data also indicate that uptake of inorganic mercury in the kidneys of rats treated with inorganic mercury plus cysteine occurred equally at both luminal and basolateral membranes. In addition, the renal uptake of mercury in rats treated with inorganic mercury plus homocysteine occurred predominantly at the basolateral membrane with some component of luminal uptake. The findings of the present study confirm that there are at least two distinct mechanisms involved in the renal uptake of inorganic mercury, with one mechanism located on the luminal membrane and the other located on the basolateral membrane. Our findings also show that cysteine and homologs of cysteine, when coadministered with inorganic mercury, greatly influence the magnitude and/or site of uptake of mercuric ions in the kidney.

scholarly journals Distribution of organic anion transporters NaDC3 and OAT1-3 along the human nephron

2016 ◽  
Vol 311 (1) ◽  
pp. F227-F238 ◽  
Author(s):  
Davorka Breljak ◽  
Marija Ljubojević ◽  
Yohannes Hagos ◽  
Vedran Micek ◽  
Daniela Balen Eror ◽  
...  
Keyword(s):  
Organic Anion ◽  
Basolateral Membrane ◽  
Human Kidney ◽  
Initial Step ◽  
Proximal Tubules ◽  
Anion Transporters ◽  
Luminal Membrane ◽  
293 Cells ◽  
Outer Stripe ◽  
S3 Segment

The initial step in renal secretion of organic anions (OAs) is mediated by transporters in the basolateral membrane (BLM). Contributors to this process are primary active Na+-K+-ATPase (EC 3.6.3.9), secondary active Na+-dicarboxylate cotransporter 3 (NaDC3/SLC13A3), and tertiary active OA transporters (OATs) OAT1/SLC22A6, OAT2/SLC22A7, and OAT3/SLC22A8. In human kidneys, we analyzed the localization of these transporters by immunochemical methods in tissue cryosections and isolated membranes. The specificity of antibodies was validated with human embryonic kidney-293 cells stably transfected with functional OATs. Na+-K+-ATPase was immunolocalized to the BLM along the entire human nephron. NaDC3-related immunostaining was detected in the BLM of proximal tubules and in the BLM and/or luminal membrane of principal cells in connecting segments and collecting ducts. The thin and thick ascending limbs, macula densa, and distal tubules exhibited no reactivity with the anti-NaDC3 antibody. OAT1–OAT3-related immunostaining in human kidneys was detected only in the BLM of cortical proximal tubules; all three OATs were stained more intensely in S1/S2 segments compared with S3 segment in medullary rays, whereas the S3 segment in the outer stripe remained unstained. Expression of NaDC3, OAT1, OAT2, and OAT3 proteins exhibited considerable interindividual variability in both male and female kidneys, and sex differences in their expression could not be detected. Our experiments provide a side-by-side comparison of basolateral transporters cooperating in renal OA secretion in the human kidney.

scholarly journals Differential localization patterns of Claudin 10, 16 and 19 in human, mouse, and rat renal tubular epithelia

2021 ◽  
Author(s):  
Caroline Prot-Bertoye ◽  
Camille Griveau ◽  
Karsten Skjødt ◽  
Lydie Cheval ◽  
Gaëlle Brideau ◽  
...  
Keyword(s):  
Tight Junction ◽  
Genetic Variations ◽  
Thick Ascending Limb ◽  
Loss Of Function ◽  
Outer Medulla ◽  
Outer Stripe ◽  
Proximal Tubular ◽  
Familial Hypomagnesemia ◽  
Weak Expression ◽  
Renal Tubular

Functional properties of the paracellular pathway depend critically on the set of claudins expressed at the tight junction. Two syndromes are causally linked to loss-of-function mutations of claudins: HELIX syndrome caused by genetic variations in the CLDN10 gene, and Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis caused by genetic variations in the CLDN16 or the CLDN19 gene. All three genes are expressed in the kidney, particularly in the thick ascending limb (TAL). However, localization of these claudins in humans and rodents remains to be delineated in detail. We studied the segmental and subcellular expression of CLDN10, 16 and 19 in both paraffin-embedded and frozen kidney sections from adult human, mouse and rat, using immunohistochemistry and immunofluorescence, respectively. Here CLDN10 was present in a subset of medullary and cortical TAL cells, localizing to basolateral domains and tight junction in human and rodent kidney. A weak expression was detected at the tight junction of proximal tubular cells. CLDN16 was primarily expressed in a subset of TAL cells in cortex and outer stripe of outer medulla, restricted to basolateral domains and tight junctional structures in both human and rodent kidney. CLDN19 predominantly colocalized with CLDN16 in tight junctions and basolateral domains of TAL but was also found in basolateral and junctional domains in more distal sites. CLDN10 expression at tight junction almost never overlapped with that of CLND16 and CLDN19, consistent with distinct junctional pathways with different permeation profiles in both human and rodent kidney.

Microperfusion study of proximal tubule bicarbonate transport in maleic acid-induced renal tubular acidosis

1986 ◽  
Vol 250 (3) ◽  
pp. F476-F482
Author(s):  
N. Bank ◽  
H. S. Aynedjian ◽  
B. F. Mutz
Keyword(s):  
Proximal Tubule ◽  
Renal Tubular Acidosis ◽  
Maleic Acid ◽  
Basolateral Membrane ◽  
Bicarbonate Transport ◽  
Mitochondrial Energy Metabolism ◽  
Before And After ◽  
Renal Tubular ◽  
Blood Transport ◽  
Acid Administration

Microperfusion studies were carried out in rats to examine the abnormality in proximal tubule HCO3- transport caused by maleic acid administration. Permeability of the proximal tubule to HCO-3 was measured by perfusing proximal tubules with a HCO3- -free low-buffer isotonic equilibrium solution containing acetazolamide after plasma [HCO3-] had been raised by intravenous NaHCO3 infusion. Insulin recovery in the collected perfusate was approximately 100% in control and maleic acid-treated rats. CO2 influx measured by microcalorimetry was not significantly different in control vs. maleic acid-treated rats. Thus maleic acid did not cause increased permeability of the proximal tubule to either inulin or HCO3-. In a second group of experiments, proximal tubule fluid and HCO3- efflux were measured in paired-reperfusion experiments before and after maleic acid administration. The perfusion fluid contained 25 mM HCO3- and 120 mM Cl-. HCO3- absorption was inhibited 25% (79 pmol/min), Na+ was inhibited 22% (164 pmol/min), and Cl- absorption (calculated as the anion gap) by 85 pmol/min. [HCO3-] in the collected perfusate rose significantly after maleic acid, presumably accompanied by a fall in [Cl-]. The observations indicate that proximal renal tubular acidosis (RTA) induced by maleic acid is characterized by impaired lumen-to-blood transport of sodium bicarbonate and chloride but not by increased backflux. Based on previously demonstrated effects of maleic acid on mitochondrial energy metabolism and cellular ATP levels, we postulate that the principal transport abnormality is impaired basolateral membrane active sodium transport, leading to a secondary reduction in brush border Na+-H+ exchange.(ABSTRACT TRUNCATED AT 250 WORDS)

AQP3, p-AQP2, and AQP2 expression is reduced in polyuric rats with hypercalcemia: prevention by cAMP-PDE inhibitors

2002 ◽  
Vol 283 (6) ◽  
pp. F1313-F1325 ◽  
Author(s):  
Weidong Wang ◽  
Chunling Li ◽  
Tae-Hwan Kwon ◽  
Mark A. Knepper ◽  
Jørgen Frøkiær ◽  
...  
Keyword(s):  
Vitamin D ◽  
Collecting Duct ◽  
Urine Osmolality ◽  
Outer Medulla ◽  
Camp Phosphodiesterase ◽  
Aqp4 Expression ◽  
Pde Inhibitors ◽  
Aqp1 Expression ◽  
Outer Stripe ◽  
Inhibitor Treatment

The purpose of this study was to evaluate whether hypercalcemia is associated with downregulation of renal aquaporins (AQPs), including AQP1, AQP2, phosphorylated AQP2 (p-AQP2), AQP3, and AQP4, and if this is the case, to test whether cAMP-phosphodiesterase (PDE) inhibitor treatment can prevent AQP downregulation and prevent the development of polyuria. Vitamin D-induced hypercalcemia in rats was associated with increased urine output and reduced urine osmolality, consistent with previous findings (Levi M, Peterson L, and Berl T. Kidney Int 23: 489–497, 1983). Semiquantitative immunoblotting revealed a significant reduction in the abundance of inner medullary AQP2 (52 ± 6% of control levels), consistent with previous studies, and of AQP2, which is phosphorylated at the PKA phosphorylation consensus site serine 256 (p-AQP2; 36 ± 8%). Moreover, AQP3 abundance was also significantly decreased (45 ± 7 and 61 ± 6% of control levels in inner medulla and whole kidney, respectively). Consistent with this, immunohistochemistry demonstrated reduced AQP3 immunolabeling along the entire collecting duct. AQP4 expression was not reduced. Surprisingly, total kidney AQP1 abundance was also reduced (60 ± 6%). AQP1 expression was reduced in the cortex and outer stripe of the outer medulla (48 ± 7%; i.e., in proximal tubules). In contrast, AQP1 levels were not changed in the inner stripe of the outer medulla or in the inner medulla (i.e., descending thin limbs and vasa recta). Treatment with the cAMP-PDE inhibitors rolipram and milrinone in combination (inhibiting PDE IV and PDE III isoenzymes) at day 2 and onward completely prevented the hypercalcemia-induced downregulation of AQP2 and AQP3 (but not AQP1) and completely prevented the development of polyuria. In conclusion, AQP3, AQP2, and p-AQP2 are downregulated and are likely to play critical roles in the development of polyuria associated with vitamin D-induced hypercalcemia. Moreover, PDE inhibitor treatment significantly prevented the reduced expression of collecting duct AQPs and prevented the development of polyuria.

scholarly journals An Immunohistochemical Investigation of Renal Phospholipidosis and Toxicity in Rats

2017 ◽  
Vol 36 (5) ◽  
pp. 386-394 ◽  
Author(s):  
Jing Ying Ma ◽  
Sandra Snook ◽  
Sheryl Garrovillo ◽  
Charles Johnson ◽  
David La
Keyword(s):  
Electron Microscopy ◽  
Membrane Protein ◽  
Kidney Injury ◽  
Tubular Epithelial Cell ◽  
Vehicle Group ◽  
Tubular Injury ◽  
Histamine H4 Receptor ◽  
Outer Stripe ◽  
H4 Receptor ◽  
Renal Tubular

Immunohistochemical staining for the lysosome-associated membrane protein 2 (LAMP-2) has been proposed previously as an alternative to electron microscopy to identify hepatic phospholipidosis. This study used LAMP-2 immunohistochemistry (IHC) to diagnose phospholipidosis in rats exhibiting renal tubular injury. Rats were administered toreforant, a histamine H4 receptor antagonist by oral gavage at a dose of 3, 10, or 100 mg/kg/d for 6 months. Hematoxylin and eosin staining revealed renal tubular epithelial cell vacuolation, hypertrophy, degeneration, and luminal dilation in the 100 mg/kg/d group animals. Renal tubular injury was confirmed using kidney injury marker 1 (KIM-1) IHC. The involvement of phosopholipidosis in the renal injury was investigated by LAMP-2. Adipophilin IHC was included to differentiate phospholipidosis from lipidosis. Increased LAMP-2 staining was observed in the 100 mg/kg/d group animals when compared to vehicle group animals. Lysosome-associated membrane protein-2 staining was most prominent in the outer stripe of the outer medulla where KIM-1 staining was also most prominent. By contrast, adipophilin staining was not increased. Phospholipidosis was also confirmed by electron microscopy. These data support the use of LAMP-2 IHC as a diagnostic tool and suggest an association between phospholipidosis and the renal tubular injury caused by toreforant.

Regulation of electrolyte and fluid secretion in salivary acinar cells

1992 ◽  
Vol 263 (6) ◽  
pp. G823-G837 ◽  
Author(s):  
B. Nauntofte
Keyword(s):  
Ionic Composition ◽  
Basolateral Membrane ◽  
Acinar Cells ◽  
Fluid Secretion ◽  
Receptor Activation ◽  
Exchange Mechanism ◽  
Luminal Membrane ◽  
Net Uptake ◽  
Cl Channels ◽  
Simultaneous Activation

The primary secretion from exocrine gland cells is a fluid rich in Na+ and Cl- with a plasmalike ionic composition. Activation of specific receptors on the plasma membrane by hormones and neurotransmitters, which leads to activation of the phosphoinositol metabolism, results in release of Ca2+ from internal Ca2+ stores. Intracellular free Ca2+ concentration ([Ca2+]i) then rises simultaneously at both the basolateral and luminal parts of the acinar cell, reaching maximum values within 1 s after stimulation. In parotid acinar cells, increased [Ca2+]i activates the opening of maxi K+ channels located on the basolateral membrane and Cl- channels presumably located on the luminal membrane, resulting in rapid loss of K+ and Cl- and water and cell shrinkage. Extracellular electroneutrality is maintained by a paracellular Na+ flux into the lumen. Because of the simultaneous activation of K+ and Cl- channels, secretion occurs at a virtually constant membrane potential of about -60 mV. After maximal muscarinic cholinergic stimulation, loss of K+, Cl-, and water results in an approximate 25% reduction in cell volume within 10-15 s after receptor activation. Concomitant with loss of Cl-, there is a loss of HCO3- from the cell, causing a decrease in intracellular pH of 0.1 pH units because of the carbonic anhydrase-mediated conversion of CO2 into H+ and HCO3-. H+ generated from the metabolism and HCO3- production is compensated for by extrusion of H+ by a Na(+)-H+ exchange mechanism, which is responsible for approximately 75% of net Na+ gain that occurs after stimulation. Increased [Na+]i activates the Na(+)-K+ pump, which in turn extrudes Na+ from the cells. In both the unstimulated and stimulated states, cellular production of HCO3- can drive a net uptake of Cl- via the Cl(-)-HCO3- exchange mechanism operating in parallel with the Na(+)-H+ exchanger. The operation of the Cl(-)-HCO3- exchanger is, together with a Na(+)-K(+)-2Cl- cotransport system, essential for maintainance of a high [Cl-]i both in the unstimulated state and during Cl- reuptake.

Prenatal and Early Postnatal Intoxication by Inorganic Mercury Resulting from the Maternal Use of Mercury Containing Soap

1987 ◽  
Vol 6 (3) ◽  
pp. 253-256 ◽  
Author(s):  
R. Lauwerys ◽  
Ch. Bonnier ◽  
Ph. Evrard ◽  
J. Ph. Gennart ◽  
A. Bernard
Keyword(s):  
Inorganic Mercury ◽  
Tubular Dysfunction ◽  
Renal Tubular Dysfunction ◽  
Lactation Period ◽  
Foetal Life ◽  
Renal Tubular ◽  
Black Boy

A case of slight renal tubular dysfunction associated with cataract and anaemia was diagnosed in a 3-month-old black boy in whom high levels of mercury were found in blood and urine. Several arguments suggest that the renal, ocular and haematological defects may have resulted from exposure to mercury during foetal life and the 1-month lactation period due to the extensive use of inorganic mercury containing cosmetics by the mother.

Temporal induction of clusterin in cisplatin nephrotoxicity.

1997 ◽  
Vol 8 (2) ◽  
pp. 302-305
Author(s):  
J R Silkensen ◽  
A Agarwal ◽  
K A Nath ◽  
J C Manivel ◽  
M E Rosenberg
Keyword(s):  
Serum Creatinine ◽  
Time Course ◽  
Tissue Injury ◽  
Kidney Tissue ◽  
Sprague Dawley ◽  
Outer Medulla ◽  
Creatinine Concentration ◽  
Cisplatin Nephrotoxicity ◽  
Tubular Necrosis ◽  
Outer Stripe

Clusterin is a ubiquitous glycoprotein induced in many organs, including the kidney, at times of tissue injury and/or remodeling. It is speculated in this study that clusterin preserves cell interactions that are otherwise perturbed by renal insults. The purpose of this study was to examine clusterin expression after cisplatin nephrotoxicity, a model characterized by a delayed time course of injury and a well-defined site of that injury (proximal tubule). Sprague-Dawley rats were treated with intravenous cisplatin (6 mg/kg) or vehicle. Serum creatinine concentrations were measured and kidneys harvested at 1, 2, and 5 days. Marked induction of clusterin mRNA was seen only at 5 days, a time when serum creatinine concentration was the highest. Histology of kidney tissue 5 days after cisplatin administration revealed marked tubular necrosis localized to the outer stripe of the outer medulla, a region rich in proximal tubules. Immunohistochemistry and in situ hybridization at 5 days demonstrated clusterin primarily in the inner stripe of the outer medulla. In conclusion, expression of clusterin follows renal injury with cisplatin at a time corresponding to the morphologic evidence of tubular necrosis and cell detachment; quite surprisingly, such expression occurs at a site distant from the primary injury.

Nephrogenic Diabetes Insipidus

1996 ◽  
Vol 17 (4) ◽  
pp. 145-146
Author(s):  
Corrine Benchimol
Keyword(s):  
Diabetes Insipidus ◽  
Nephrogenic Diabetes Insipidus ◽  
Collecting Duct ◽  
Basolateral Membrane ◽  
Duct Cell ◽  
Cell Binding ◽  
Luminal Membrane ◽  
Concentrate Urine ◽  
V2 Receptor ◽  
Final Effect

Nephrogenic diabetes insipidus (NDI) is a disorder, either congenital or acquired, in which antidiuretic hormone (ADH) secretion is normal, but the ability to concentrate urine is reduced because of insensitivity of the collecting tubule to ADH. The antidiuretic action of arginine vasopressin requires binding of the hormone to the renal type V2 receptor on the basolateral membrane of the collecting duct principal cell. Binding results in activation of adenylate cyclase, generation of cAMP, and increased reabsorption of water across the apical membrane of the renal collecting duct cell. The defect in NDI may be located at any of the steps from binding of vasopressin to the final effect of the hormone on the luminal membrane.

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