Renal secretion of amino acids in ophidian reptiles

1986 ◽  
Vol 250 (4) ◽  
pp. R712-R720 ◽  
Author(s):  
S. Benyajati ◽  
W. H. Dantzler
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Tubular Secretion ◽  
Cysteic Acid ◽  
Thamnophis Sirtalis ◽  
Renal Secretion ◽  
Renal Tubular Secretion ◽  
Beta Alanine ◽  
Renal Tubular ◽  
Filtered Load

Net renal tubular secretion of endogenous beta-amino acids (taurine, beta-alanine, beta-aminoisobutyric acid) and their endogenous analogue (L-cysteic acid) was revealed in the olive sea snake, Aipysurus laevis, and in the garter snake, Thamnophis sirtalis, by renal clearance methods. The net secretory rates ranged from 16 to 795 nmol X kg-1 X h-1, with taurine being secreted at the highest rates. These rates of secretion are comparable to those observed in marine fish, the only other group of vertebrates exhibiting renal tubular secretion of L-amino acids under physiological conditions. However, only some snakes (8-58%) demonstrated net tubular secretion; the others (0-58%) showed net tubular reabsorption of these amino acids. Net tubular secretion was consistently observed whenever the filtered load of the amino acid was low, and net reabsorption was apparent whenever the filtered load was high; the two variables being significantly correlated. An analysis of the net amino acid transport rates, both secretory and reabsorptive, as a function of the filtered load suggests that in snakes the beta-amino acids are reabsorbed and secreted at discrete tubular sites, with the secretory sites located beyond the major reabsorptive sites. Taurine, beta-alanine, and L-cysteic acid appear to share a common transport system in the snake renal tubule cells.

scholarly journals Effect of Probenecid on the Renal Excretion Mechanism of a New Carbapenem, DA-1131, in Rats and Rabbits

1999 ◽  
Vol 43 (1) ◽  
pp. 96-99 ◽  
Author(s):  
So H. Kim ◽  
Won B. Kim ◽  
Myung G. Lee
Keyword(s):  
Body Weight ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Renal Excretion ◽  
Anion Transport ◽  
Tubular Secretion ◽  
Renal Secretion ◽  
Renal Tubular Secretion ◽  
Transport Inhibitor ◽  
Renal Tubular

ABSTRACT The effects of probenecid, an anion transport inhibitor, on the renal excretion mechanism of a new anionic carbapenem, DA-1131, were investigated after a 1-min intravenous infusion of DA-1131 at 100 mg/kg of body weight to rabbits and 50 mg/kg to rats with or without probenecid at 50 mg/kg for both species. In control rabbits, the renal clearance (CLR) of DA-1131 and the glomerular filtration rate based on creatinine clearance (CLCR) were 6.14 ± 2.09 and 2.26 ± 0.589 ml/min/kg, respectively. When considering the less than 10% plasma protein binding of DA-1131 in rabbits, renal tubular secretion of DA-1131 was observed in rabbits. The CLR of DA-1131 (3.87 ± 0.543 ml/min/kg) decreased significantly with treatment with probenecid in rabbits, indicating that the renal tubular secretion of DA-1131 was inhibited by probenecid. However, in control rats, the CLR of DA-1131 (5.80 ± 1.94 ml/min/kg) was comparable to the CLCR(4.29 ± 1.64 ml/min/kg), indicating that DA-1131 was mainly excreted by glomerular filtration in rats. Therefore, it could be expected that the CLR of DA-1131 could not be affected by treatment with probenecid in rats; this was proved by a similar CLR of DA-1131 with treatment with (6.93 ± 0.675 ml/min/kg) or without (5.80 ± 1.94 ml/min/kg) probenecid. Therefore, the renal secretion of DA-1131 is a factor in rabbits but is not a factor in rats.

Purification of Antihemophilic Factor (Factor VIII) by Amino Acid Precipitation*

1964 ◽  
Vol 11 (01) ◽  
pp. 064-074 ◽  
Author(s):  
Robert H Wagner ◽  
William D McLester ◽  
Marion Smith ◽  
K. M Brinkhous
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Factor Viii ◽  
Plasma Protein ◽  
Acid Precipitation ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Specific Procedure ◽  
Beta Alanine ◽  
Antihemophilic Factor

Summary1. The use of several amino acids, glycine, alpha-aminobutyric acid, alanine, beta-alanine, and gamma-aminobutyric acid, as plasma protein precipitants is described.2. A specific procedure is detailed for the preparation of canine antihemophilic factor (AHF, Factor VIII) in which glycine, beta-alanine, and gammaaminobutyric acid serve as the protein precipitants.3. Preliminary results are reported for the precipitation of bovine and human AHF with amino acids.

scholarly journals Amino acid production in isolated rat liver mitochondria

1973 ◽  
Vol 134 (2) ◽  
pp. 431-436 ◽  
Author(s):  
W. Ferdinand ◽  
W. Bartley ◽  
V. Broomhead
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Composition ◽  
Acid Composition ◽  
Lipid Hydroperoxide ◽  
Liver Mitochondria ◽  
Cysteic Acid ◽  
Rat Liver Mitochondria ◽  
Isolated Mitochondria ◽  
Selective Retention

Amino acid analyses of mitochondrial membranes are compared with the amino acid composition of whole mitochondria (Alberti, 1964) and found to be very similar except in the cystine content. The composition of the endogenous amino acids found in freshly prepared mitochondria has been established and shown to differ considerably from the amino acid composition of membranes or whole mitochondria. The amino acids produced during anaerobic incubation of mitochondria at pH7.4, on the other hand, resemble the membrane in composition, supporting the view that neutral proteinase activity is responsible for their appearance. Aerobic incubation produces a similar pattern of amino acids except that amino acids such as proline, serine, asparagine, glutamic acid and glutamine, which can be metabolically utilized under aerobic conditions, are present to a smaller extent. The presence of large relative concentrations of endogenous taurine, cysteic acid and oxidized glutathione and the accumulation of taurine during incubation is found. The selective retention of taurine and cysteic acid within the mitochondria is established. It is proposed that the first step in the degeneration of isolated mitochondria results from lipid hydroperoxide accumulation caused by the lack of glutathione reductase in isolated mitochondria.

Abstract 14035: Renal Tubular Secretion and Cardiac Distribution of Dofetilide is Dependent on MATE1 Function

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Muhammad Erfan Uddin ◽  
Yan Jin ◽  
Alice A Gibson ◽  
Ingrid M Bonilla ◽  
Cynthia A Carnes ◽  
...  
Keyword(s):  
Organic Cation ◽  
Tubular Secretion ◽  
Hek293 Cells ◽  
Delayed Rectifier ◽  
Organic Cation Transporters ◽  
Wild Type ◽  
Renal Tubular Secretion ◽  
Cation Transporters ◽  
Renal Tubular

Introduction: Dofetilide is a delayed rectifier potassium channel inhibitor used to treat patients with atrial fibrillation and flutter, and its use is associated with a risk of QT prolongation and Torsades de Pointes . The mechanisms involved in dofetilide’s renal tubular secretion and its uptake into cardiomyocytes remain unknown. Previously reported drug-drug interaction (DDI) studies suggest the involvement of organic cation transporters. Here, we investigated the contribution of organic cation transporters (OCT2 and MATE1) to the pharmacokinetics of dofetilide to gain insight into its DDI potential. Hypothesis: Based on known DDIs with dofetilide, we hypothesize that OCT2 and/or MATE1 play a key role in the inter-individual variability in pharmacokinetics and pharmacodynamics of dofetilide. Methods: In vitro and ex vivo transport kinetics of dofetilide were determined in HEK293 cells stably transfected with OCT2 or MATE1, and in isolated cardiomyocytes, respectively. In vivo studies were performed in wild-type, OCT2-, and MATE1-deficient mice (n=5) receiving dofetilide (5 mg/kg, p.o., 2.5 mg/kg, i.v.), with or without several contraindicated drugs. Dofetilide concentrations in plasma and urine were determined by UPLC-MS/MS. Results: In vitro studies demonstrated that dofetilide is a good substrate of MATE1 but not OCT2. Deficiency of MATE1 was associated with increased plasma concentrations of dofetilide and with a significantly reduced urinary excretion (3-fold in females and 5-fold in males, respectively). Dofetilide accumulation in cardiomyocytes was increased by 2-fold in MATE1-deficient females, and pre-incubation with the MATE1 inhibitor cimetidine significantly reduced dofetilide uptake in wild-type cardiomyocytes. Several contraindicated drugs listed in the dofetilide prescribing information, including cimetidine, ketoconazole, increased dofetilide plasma exposure in wild-type mice by >2.8-fold. Conclusion: Renal secretion of dofetilide is mediated by MATE1 and is highly sensitive to inhibition by many widely used prescription drugs that can cause clinically relevant DDIs. Deficiency of MATE1 also increases accumulation in the heart which may contribute to individual variation in response to dofetilide.

Renal tubular secretion of organic anions

1997 ◽  
Vol 25 (2-3) ◽  
pp. 217-230 ◽  
Author(s):  
William H. Dantzler ◽  
Stephen H. Wright
Keyword(s):  
Organic Anions ◽  
Tubular Secretion ◽  
Renal Tubular Secretion ◽  
Renal Tubular

Renal Tubular Transport of Amino Acids

1971 ◽  
Vol 17 (4) ◽  
pp. 245-266 ◽  
Author(s):  
John Atherton Young ◽  
Benedict Sol Freedman
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Proximal Tubule ◽  
Amino Nitrogen ◽  
High Capacity ◽  
High Specificity ◽  
Brush Borders ◽  
Tubular Transport ◽  
Renal Tubular Transport ◽  
Renal Tubular

Abstract Cushny in 1917 first remarked on the extensive amino acid reabsorption which occurs in the nephron. Although many workers since then have studied the nature and localization of the reabsorptive mechanism, progress has been slow because of the technical difficulties of micropuncture work. The bulk of filtered amino nitrogen is reabsorbed in the proximal tubule although the possibility of there being more distal reabsorptive (or secretory) sites cannot be excluded. It is also uncertain whether all segments of the proximal tubule contribute equally to the reabsorptive process. Amino acid reabsorption is an active process involving numerous illdefined steps, the first of which is binding to the brush borders. Renal amino acid transport mechanisms are of two kinds: the high-capacity low-specificity systems transport whole groups of amino acids—the acidic, basic, neutral, and imino-glycine groups—while the other, the low-capacity high-specificity systems, transport single or perhaps pairs of amino acids only.

Interactions of neutral and acidic amino acids in renal tubular transport

1962 ◽  
Vol 202 (3) ◽  
pp. 577-583 ◽  
Author(s):  
William A. Webber
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Plasma Concentrations ◽  
Side Chain ◽  
Neutral Amino Acids ◽  
Acidic Amino Acids ◽  
Renal Tubular Reabsorption ◽  
Renal Tubular Transport ◽  
Renal Tubular ◽  
Amino Acid Concentrations

The effects of intravenous infusions of a variety of neutral and acidic amino acids on the plasma concentrations and excretions of naturally occurring amino acids were studied in dogs. Conventional clearance techniques were used, and the amino acid concentrations were determined by ion exchange column chromatography. Infusion of either l-glutamic acid or l-aspartic acid caused a gross increase in the plasma concentration and excretion of the other. Infusions of neutral amino acids including glycine, l-alanine, l-leucine, l-methionine, l-proline, and l-phenylalanine caused some minor changes in the endogenous plasma amino acid concentrations. They produced increases in the excretion of other neutral amino acids and, in some cases, of acidic and basic amino acids as well. In general, amino acids with long side chains were most effective in inhibiting reabsorption while cyclic side-chain compounds were less effective. There appear to be at least three somewhat separable mechanisms for renal tubular reabsorption of amino acids in dogs.

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