Structure-Affinity Relationship of Different Drugs at the Contraluminal Transport System for Organic Cations in Proximal Tubules of Rat Kidneys

2015 ◽  
pp. 26-29
Author(s):  
Edgar Br�ndle ◽  
Joachim Greven
Keyword(s):  
Transport System ◽  
Proximal Tubules ◽  
Organic Cations ◽  
Relationship Of ◽  
Rat Kidneys

scholarly journals Differential regulation of B/K protein expression in proximal and distal tubules of rat kidneys with ischemia-reperfusion injury

2007 ◽  
Vol 292 (1) ◽  
pp. F100-F106 ◽  
Author(s):  
Ki-Hwan Han ◽  
U-Young Lee ◽  
Yoon-Seong Jang ◽  
Yoon Mi Cho ◽  
Young Min Jang ◽  
...  
Keyword(s):  
Protein Expression ◽  
Cellular Localization ◽  
Collecting Duct ◽  
Ischemia Reperfusion ◽  
Proximal Tubules ◽  
Epithelial Cell Line ◽  
Thick Ascending Limb ◽  
S3 Segment ◽  
Distal Tubules ◽  
Rat Kidneys

Brain/kidney (B/K) protein is a novel double C2-like-domain protein that is highly expressed in rat brain and kidney, but its cellular localization and functional role in the kidney are still undetermined. We examined the cellular localization of B/K protein in the rat kidney under normal and ischemic conditions. Ischemia-reperfusion (I/R) injury was induced by clamping both renal arteries for 45 min, and animals were killed at 1 and 6 h and 1, 2, 3, 5, 7, 14, and 28 days after the reperfusion. Kidney tissues were processed for immunohistochemistry and immunoblot analyses using rabbit anti-B/K polyclonal antibodies. In control kidneys, B/K protein was expressed primarily in distal tubules including the thick ascending limb, distal convoluted and connecting tubules, and collecting duct. Notably, B/K protein was also expressed in the straight portion (S3 segment), but not in the S1 or S2, of proximal tubules, and podocytes of the glomerulus. In rat kidneys with I/R injury, expression of B/K protein was differentially regulated according to the anatomic location. In distal tubules, overall expression of B/K protein was markedly decreased. On the other hand, I/R injury significantly increased B/K protein expression in the S3 segment of the outer medulla as well as in the rat proximal tubular epithelial cell line NRK-52E in vitro. Furthermore, B/K protein was strongly expressed in many exfoliated cells in the lumen and urine. These findings suggest that B/K protein is closely associated with cell death in proximal tubules, which are vulnerable to I/R injury in the kidney.

scholarly journals Endogenous dopamine regulates phosphate reabsorption but not NaK-ATPase in spontaneously hypertensive rat kidneys.

1994 ◽  
Vol 5 (4) ◽  
pp. 1125-1132
Author(s):  
A Debska-Slizien ◽  
P Ho ◽  
R Drangova ◽  
A D Baines
Keyword(s):  
Spontaneously Hypertensive Rat ◽  
Membrane Vesicle ◽  
Proximal Tubules ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Endogenous Dopamine ◽  
Hypertensive Rat ◽  
Wistar Kyoto ◽  
Signaling Process ◽  
Rat Kidneys

Dopamine's modulatory actions on signal transduction in the spontaneously hypertensive rat (SHR) proximal tubule are blunted; therefore, it was predicted that dopamine does not regulate phosphate (Pi) reabsorption in SHR. To test this hypothesis, dopamine production was inhibited with carbidopa (10 mg/kg ip) 18 h before and during clearance measurements of chronically denervated SHR and Wistar-Kyoto (WKY) rat kidneys. Dopamine excretion decreased 80% from SHR and 85% from WKY rats. Pi excretion decreased 60 to 67%. Plasma Pi and calcium, inulin clearance, and Na excretion did not change. Citrate excretion, which reflects proton secretion by proximal tubules, decreased 72% from WKY rats. Citrate excretion was significantly lower from SHR (5 +/- 10 pmol/min) than from WKY rats (73 +/- 11 pmol/min) and was not altered by carbidopa. Carbidopa, injected 18 and 1 h before kidneys were collected, increased NaK-ATPase in cortical basolateral membranes from WKY rats (27%) but not in membranes from SHR. After the incubation of renal cortical minceates for 15 min with L-DOPA (10(-5) M), there was no change in brush border membrane vesicle uptake of 32Pi, (3H)glucose, or (14C)citrate. Incubation with carbidopa (10(-4) M) increased 32Pi uptake by 11% (P < 0.001) and (3H)glucose uptake by 9% (P = 0.02). (14C)citrate uptake was not increased by carbidopa but was higher in SHR (977 +/- 2 pmol/10 s.mg) than in WKY rats (823 +/- 43 pmol/10 s.mg; P = 0.04). In summary, dopamine produced in WKY rat and SHR proximal tubules decreases Pi uptake by using a signaling process distinct from those that regulate NaK-ATPase and the antiporter.(ABSTRACT TRUNCATED AT 250 WORDS)

Expression of Na-P(i) cotransport in rat kidney: localization by RT-PCR and immunohistochemistry

1994 ◽  
Vol 266 (5) ◽  
pp. F767-F774 ◽  
Author(s):  
M. Custer ◽  
M. Lotscher ◽  
J. Biber ◽  
H. Murer ◽  
B. Kaissling
Keyword(s):  
Transport System ◽  
Polyclonal Antibodies ◽  
Rat Kidney ◽  
Proximal Tubules ◽  
Expression Cloning ◽  
Kidney Cortex ◽  
Thick Ascending Limb ◽  
Rt Pcr ◽  
Rat Kidney Cortex ◽  
Proximal Tubular

We have recently identified a rat kidney cortex Na-dependent transport system for phosphate (P(i)) by expression cloning (NaP(i)-2) (S. Magagnin, A. Werner, D. Markovich, V. Sorribas, G. Stange, J. Biber, and H. Murer. Proc. Natl. Acad. Sci. USA 90: 5979, 1993). In this study we have used reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry to establish the sites of expression of the NaP(i)-2-related mRNA and protein. RT-PCR was performed with single microdissected nephron segments. From these experiments we conclude that NaP(i)-2 mRNA is predominantly expressed in the proximal tubules of superficial and deep nephrons. No NaP(i)-2 mRNA was detected in the thick ascending limb of Henle's loop; however, faint NaP(i)-2 related PCR products were also observed in collecting ducts. Expression of the NaP(i)-2 protein was examined with the use of polyclonal antibodies raised against synthetic NaP(i)-2-derived peptides. Strong specific anti-NaP(i)-2 antiserum-mediated immunofluorescence was found in the convoluted part of proximal tubules and gradually decreased along the straight part. Immunofluorescence indicated that the NaP(i)-2 protein is present in the brush border of proximal tubular cells. In addition, NaP(i)-2-specific immunofluorescence was also observed in subapical vesicles. The described distribution of the NaP(i)-2 protein is in agreement with previously described nephron sites of P(i) reabsorption in the rat kidney and therefore suggests that the NaP(i)-2 transport system represents an Na-P(i) cotransporter involved in proximal tubular apical transport of phosphate.

cAMP-stimulated cation cotransport in avian erythrocytes: inhibition by "loop" diuretics

1980 ◽  
Vol 238 (3) ◽  
pp. C139-C148 ◽  
Author(s):  
H. C. Palfrey ◽  
P. W. Feit ◽  
P. Greengard
Keyword(s):  
Transport System ◽  
Loop Diuretics ◽  
Intracellular Camp ◽  
Sequence Of Events ◽  
Avian Erythrocytes ◽  
Avian Erythrocyte ◽  
Cotransport System ◽  
Diuretic Potency ◽  
Relationship Of ◽  
Related Compounds

The effect of a series of diuretically active substituted 3-aminobenzoic acid derivatives and related compounds was investigated on a cyclic AMP-activated Na+-K+ cotransport system in avian erythrocytes. A good correlation between the diuretic potency of this class of "loop" diuretics in the dog and their inhibition of cation cotransport in turkey erythrocytes was found. Selected thiazide-type diuretics were found to be ineffective. The most active compound tested (3-benzylamino-4-phenylthio-5-sulfamoylbenzoic acid) had an effective dose50 of 4.6 x 10(-8) M in the avian system, and was about 5 times more potent than bumetanide and 500 times more potent than furosemide in this regard. The diuretics appear to interact directly with the cation transport system itself, and not with some antecedent step in the sequence of events from intracellular cAMP accumulation to stimulation of transport. The compounds tested did not appear to compete at Na+- or K+-binding sites on the transport system. The similarity in the structure-activity relationship of these agents in the avian erythrocyte and the kidney suggests that the avian erythrocyte may be a useful model for analysis both of the diuretic-sensitive transport system of the mammalian kidney, and of the molecular mechanism of loop diuretic action.

Depolarization-induced alkalinization in proximal tubules. II. Effects of lactate and SITS

1989 ◽  
Vol 256 (2) ◽  
pp. F354-F365 ◽  
Author(s):  
A. W. Siebens ◽  
W. F. Boron
Keyword(s):  
Intracellular Ph ◽  
Transport System ◽  
Proximal Tubules ◽  
Disulfonic Acid ◽  
Ambystoma Tigrinum ◽  
Tiger Salamander ◽  
Organic Substrates ◽  
Preceding Study ◽  
Lines Of Evidence

Intracellular pH and voltage microelectrodes were used to further characterize the depolarization-induced alkalinization (DIA) observed in isolated perfused proximal tubules of the tiger salamander Ambystoma tigrinum. Tubules were depolarized by raising basolateral [K+] from 2.5 to 50 mM. The solutions were air equilibrated and nominally HCO3- free (estimated [HCO3-] = 0.2 mM). In the preceding study we showed that the DIA is partially blocked by removal of Na+ from only the lumen or only the bath, but completely blocked by bilateral Na+ removal. In the present study we found that bilateral amiloride (1 mM) had no effect on the DIA, suggesting that Na-H exchange is not involved. In contrast, basolateral 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS) (0.5 mM) partially blocked the DIA, presumably due to inhibition of one or more of three SITS-sensitive basolateral transporters present in amphibian proximal tubules: electrogenic Na-HCO3 cotransport, Na-dependent Cl-HCO3 exchange, and H-lactate cotransport. Bilateral removal of all organic substrates, or of only lactate (Lac-) also blocked the DIA partially. As shown elsewhere (A. W. Siebens, and W. F. Boron, J. Gen. Physiol. 90: 799-831, 1987), in the absence of depolarization, luminal Lac- causes a pHi increase due to luminal Lac- entry via a Na-Lac cotransporter, followed by basolateral Lac- exit via an H-Lac cotransporter sensitive to alpha-cyano-4-hydroxycinnamate (CHC). Three lines of evidence indicate that this Na-Lac/H-Lac mechanism is involved in the DIA. 1) As noted previously, the DIA is partially blocked by luminal Na+ removal. 2) With the DIA partially blocked by basolateral SITS, removal of Lac- from only the lumen blocks the remainder of the DIA. 3) Basolateral CHC partially blocks the DIA. Our data suggest that the DIA is mediated by at least two additive mechanisms, a basolateral transporter that is SITS sensitive and Na+ dependent, and the Na-Lac/H-Lac transport system.

Relationship of Electrical Potential Differences to Net Ion Fluxes in Rat Proximal Tubules

Nature ◽  
1964 ◽  
Vol 201 (4920) ◽  
pp. 714-715 ◽  
Author(s):  
DONALD MARSH ◽  
SIDNEY SOLOMON
Keyword(s):  
Electrical Potential ◽  
Proximal Tubules ◽  
Ion Fluxes ◽  
Relationship Of

scholarly journals Building a model of a problem situation in transport systems

2022 ◽  
Vol 14 (2) ◽  
pp. 4-9
Author(s):  
Viktor Aulin ◽  
◽  
Dmitrо Golub ◽  
Viktor Bilichenko ◽  
Artem Zamurenko ◽  
...  
Keyword(s):  
Decision Making ◽  
Transport System ◽  
Block Diagram ◽  
A Priori ◽  
Transport Systems ◽  
Problem Situation ◽  
Efficiency Criterion ◽  
Relationship Of ◽  
The Relationship ◽  
Selection Of

The approach to construction of model of a problem situation in transport system is resulted, the block diagram of its algorithm is developed. It is revealed that the transition stage from the problem to the formulation of formal tasks is a problem situation, and the tasks can be solved in different ways, forming a set of strategies. It is noted that in the general case the result of operations is uncertain, which is caused by the uncertainty of the conditions of the operation and the action of factors of different nature. It is revealed that the acquisition of values of indicators that characterize one or another result of the operation is associated with the solution of the problem of modeling operations. The stages of the problem of studying the efficiency of the operation in the transport system are given. A number of assumptions are made about the process of obtaining results, which is associated with the formation of the operation model and obtaining efficiency estimates based on modeling results, as well as the process of analyzing the results, which involves solving the selection problem based on the established efficiency criterion or system of such criteria. It is found that the model of the problem situation in transport systems reflects the relationship of the main elements of the decision-making process and the sequence of formation of partial tasks and is built to cover the problem of decision-making as a whole, to present its main elements to be finalized. about the strategy of the operation. It is shown that the presence of a certain component as an independent element in the model of the problem situation assumes that the set of values of uncertain factors in the development of solutions will be either set externally, or finding these values will be an independent task. A list of actions for solving partial problems based on this model is presented. It is shown that in many practical cases it is observed that the a priori task of one of the main criteria of efficiency leads to the selection of some set of alternatives. Therefore, the choice of the best alternative requires the formation of a compound criterion, which includes both formal and informal prescriptions for making a judgment on the basis of which the selection or return and correction of elements of the model of the problem situation.

Procainamide transport in rabbit renal cortical brush border membrane vesicles

1985 ◽  
Vol 249 (4) ◽  
pp. F532-F541 ◽  
Author(s):  
T. D. McKinney ◽  
M. E. Kunnemann
Keyword(s):  
Cell Membrane ◽  
Brush Border ◽  
Brush Border Membrane ◽  
Apical Cell ◽  
Membrane Vesicles ◽  
Brush Border Membrane Vesicles ◽  
Proximal Tubules ◽  
Ammonium Ion ◽  
Organic Cations ◽  
Apical Cell Membrane

Previous studies in canine and rat renal cortical brush border membrane vesicles (BBMV) and some results in isolated perfused rabbit proximal tubules indicate that organic cations may be transported across the apical cell membrane by an organic cation/proton exchange process. To determine more directly whether organic cations are transported across the apical cell membrane of rabbit proximal tubules, [3H]procainamide uptake in BBMV was studied. Procainamide uptake was linearly related to the inverse of the media osmolarity, indicating uptake into an intravesicular space. A proton gradient directed from vesicle interior outwardly stimulated and an opposite gradient inhibited procainamide uptake. pH-stimulated uptake was inhibited by the proton ionophore carbonyl cyanide p-trifluoromethoxyphenyl hydrazone (FCCP) and was also reduced by an inwardly directed sodium gradient. pH-stimulated procainamide uptake was inhibited by other organic cations including the quarternary ammonium ion tetramethylammonium, indicating that the effect of proton gradients was not due to changes in nonionic diffusion. pH-stimulated procainamide uptake at 10 s was saturable with an apparent Km of 5.4 X 10(-4) M and Vmax of 4.7 X 10(-10) mol X mg protein-1. Uptake of [3H]procainamide was enhanced when BBMV were preloaded with nonradioactive procainamide but this was prevented by FCCP and valinomycin. Finally, an outwardly directed potassium gradient in the presence of valinomycin failed to significantly stimulate procainamide uptake. These results are consistent with a mechanism of secretion that involves electroneutral exchange of procainamide for protons across the apical cell membrane of rabbit proximal tubules.

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