scholarly journals Metabolism of glycine- and hydroxyproline-containing peptides by the isolated perfused rat kidney

1985 ◽  
Vol 229 (2) ◽  
pp. 545-549 ◽  
Author(s):  
M Lowry ◽  
D E Hall ◽  
J T Brosnan
Keyword(s):  
Amino Acids ◽  
Rat Kidney ◽  
Isolated Perfused Rat Kidney ◽  
Perfused Rat Kidney ◽  
Rat Kidneys

Isolated perfused rat kidneys removed considerable quantities of glycyltyrosine, glycylhydroxyproline, tetraglycine and prolylhydroxyproline from the perfusate. The component amino acids are released into the perfusate and, in the case of the glycine-containing peptides, there is increased synthesis of serine. Removal of peptides was more than could be accounted for on the basis of filtration, so antiluminal metabolism is indicated. Metabolism of such peptides by the kidney may contribute to renal serine synthesis in vivo.

Nitric oxide enhancement of erythropoietin production in the isolated perfused rat kidney

1995 ◽  
Vol 269 (4) ◽  
pp. C917-C922 ◽  
Author(s):  
K. Yoshioka ◽  
J. W. Fisher
Keyword(s):  
Nitric Oxide ◽  
Rat Kidney ◽  
Mrna Levels ◽  
Isolated Perfused Rat Kidney ◽  
Intracellular Cgmp ◽  
Perfused Rat Kidney ◽  
Arterial Po2

We have previously reported that nitric oxide (NO) and guanosine 3',5'-cyclic monophosphate (cGMP) may be involved in the regulation of erythropoietin (Epo) production in response to hypoxia both in vivo and in vitro (20). In the present studies, we have used the isolated perfused rat kidney to assess the role of NO in oxygen sensing and Epo production. When arterial PO2 was reduced from 100 mmHg (normoxemic) to 30 mmHg (hypoxemic) in the perfusate of this system, perfusate levels of Epo were significantly increased. This hypoxia-induced increase in Epo production was significantly decreased by the addition of NG-nitro-L-arginine methyl ester (L-NAME; 1 mM) to the perfusates. Hypoxemic perfusion also produced a significant increase, and L-NAME significantly inhibited this increase, in intracellular cGMP levels in the kidney when compared with normoxemic perfused kidneys. Quantitative reverse transcription-polymerase chain reaction also revealed that hypoxemic perfusion produced significant increases in Epo mRNA levels in the kidney, which was blocked by L-NAME. Our findings further support an important role for the NO/cGMP system in hypoxic regulation of Epo production.

Effects of atrial natriuretic peptides on metabolism of arginine vasopressin by isolated perfused rat kidney

1992 ◽  
Vol 263 (2) ◽  
pp. R273-R278
Author(s):  
M. R. Lebowitz ◽  
A. M. Moses ◽  
S. J. Scheinman
Keyword(s):  
Arginine Vasopressin ◽  
Rat Kidney ◽  
Fractional Excretion ◽  
Metabolic Clearance ◽  
Isolated Perfused Rat Kidney ◽  
Perfused Rat Kidney ◽  
Clearance Receptor ◽  
Atrial Natriuretic

Atrial natriuretic peptide (ANP) antagonizes the release and action of arginine vasopressin (AVP) both in vivo and in vitro. We have reported that ANP increases the urinary and metabolic clearances of AVP in normal subjects (A. M. Moses et al. J. Clin. Endocrinol. Metab. 70: 222-229, 1990). To clarify this effect, we perfused isolated rat kidneys in vitro and measured the clearances of AVP for 30 min after the addition of rat ANP [rANP-(1-28), 10(-7) M]. In the perfused kidney, rANP increased the urinary clearance of AVP (UCAVP) from 321 +/- 19 to 417 +/- 20 microliters/min (P less than 0.01) and increased the glomerular filtration rate (GFR) from 558 +/- 28 to 696 +/- 28 microliters/min (P less than 0.01). Fractional excretion of AVP was unchanged. Rates of AVP reabsorption were directly related to filtered AVP, and this relationship was not altered by ANP. ANP did not affect the total organ clearance or the renal metabolic clearance of AVP. The increase in GFR was associated with increases in renal vascular resistance (P less than 0.05), filtration fraction (P less than 0.01), and sodium excretion (P less than 0.001). UCAVP also increased when GFR was raised without ANP by perfusing at higher pressures. The rat ANP clearance receptor agonist [cANP- (4-23), 10(-7) M] did not change GFR or UCAVP. ANP increases UCAVP in the isolated perfused rat kidney. This appears to be a hemodynamic effect of ANP, acting through its biological receptor and not the clearance receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Cystine and lysine reabsorption in the isolated perfused rat kidney

1989 ◽  
Vol 256 (5) ◽  
pp. F901-F908
Author(s):  
K. A. Roby ◽  
S. Segal
Keyword(s):  
Transport System ◽  
Brush Border ◽  
Rat Kidney ◽  
Isolated Perfused Rat Kidney ◽  
Transport Studies ◽  
Perfused Rat Kidney ◽  
Renal Tubular Reabsorption ◽  
Renal Tubular

Renal tubular reabsorption of cystine and lysine were studied in the isolated perfused rat kidney to bridge the gap between in vivo clearance studies, and in vitro transport studies of tubule fragments, cells, and brush-border membranes. Lysine was reabsorped by a saturable transport system shared by the dibasics. Cystine was also reabsorbed by a saturable transport system, which was shared in part by the dibasics (maximum inhibition 30%). The lysine threshold (Fmin) was 0.9 mumol.min-1.g-1, with a tubular maximum (TM) of 2.4 mumol.min-1.g-1. The cystine Fmin was 0.06 mumol.min-1.g-1; the TM could not be estimated because it was above the limit of cystine solubility. There was no evidence of cystine ,secretion.- The gamma-glutamyltransferase inhibitor, AT-125, decreased cystine excretion, but only in the presence of glutathione, glycine, glutamate, and the diabasic amino acids. This suggests that cystine from glutathione degradation at the brush border may contribute to urinary cystine (an explanation of the phenomenon of cystine secretion), but only under certain conditions.

scholarly journals Renal Disposition of Colistin in the Isolated Perfused Rat Kidney

2009 ◽  
Vol 53 (7) ◽  
pp. 2857-2864 ◽  
Author(s):  
Zheng Ma ◽  
Jiping Wang ◽  
Roger L. Nation ◽  
Jian Li ◽  
John D. Turnidge ◽  
...  
Keyword(s):  
Rat Kidney ◽  
Tubular Reabsorption ◽  
Mean Values ◽  
Isolated Perfused Rat Kidney ◽  
Renal Disposition ◽  
Perfused Rat Kidney ◽  
Renal Clearances ◽  
The Mean ◽  
Potential Inhibitors

ABSTRACT Nephrotoxicity is an important limitation to the clinical use of colistin against Pseudomonas aeruginosa and other gram-negative pathogens. Previous work reported net tubular reabsorption of colistin by the kidney in vivo, but there is no knowledge of its disposition within the kidney. This study investigated the renal disposition and potential transport mechanisms of colistin in the isolated perfused rat kidney (IPK) model by perfusing with colistin sulfate alone (2 μg/ml) or in the presence of potential inhibitors (tetraethylammonium [TEA], glycine-glycine [Gly-Gly], or hydrochloric acid [HCl]) at three different concentrations. When perfused alone, the renal clearances (CLR) for colistin A and B (the major components of colistin) in control kidneys were constant and low (mean values < 0.05 ml/min throughout the perfusion). The mean clearance ratios [CR, defined as CLR/(f u × GFR), where f u is the fraction of drug unbound in perfusate and GFR is the glomerular filtration rate] were significantly less than 1. It was concluded that there is net tubular reabsorption of colistin, and this exceeded the reabsorption of water. Less than 10% eliminated from perfusate was recovered in urine, suggesting considerable renal accumulation of colistin. The CR values for colistin were significantly increased when perfused with TEA (500 μM), Gly-Gly (833 μM), and HCl (2,500, 5,000, and 10,000 μM). It is proposed that renal reabsorption of colistin may involve organic cation transporters (inhibited by TEA) and peptide transporters (inhibited by Gly-Gly) and that the process is sensitive to the pH of urine.

scholarly journals Enhanced reabsorption of bicarbonate and phosphorus by the addition of amino acids in the isolated perfused rat kidney

1985 ◽  
Vol 27 (6) ◽  
pp. 951-953 ◽  
Author(s):  
Norihiko Terao ◽  
Muneya Suzuki ◽  
Yasushi Asano ◽  
Saichi Hosoda
Keyword(s):  
Amino Acids ◽  
Rat Kidney ◽  
Isolated Perfused Rat Kidney ◽  
Perfused Rat Kidney

Metabolism of neurotensin by isolated perfused rat kidney

1990 ◽  
Vol 258 (6) ◽  
pp. E930-E936
Author(s):  
D. J. Gillatt ◽  
A. Shulkes ◽  
D. M. Read ◽  
K. J. Hardy
Keyword(s):  
Half Life ◽  
High Performance ◽  
Rat Kidney ◽  
Biologically Active ◽  
In Vivo Studies ◽  
Minor Role ◽  
Renal Elimination ◽  
Isolated Perfused Rat Kidney ◽  
Perfused Rat Kidney

Studies in humans and conscious animals have established that the kidney is a key organ involved in the clearance of the brain-gut peptide neurotensin (NT). However, these in vivo studies cannot determine the mechanisms involved in the renal elimination of NT. We have therefore used the isolated perfused rat kidney preparation, which enables renal elimination to be studied in isolation from other organs. NT was measured with both COOH-terminal (biologically active end) and NH2-terminal (biologically active end) directed antisera. NT was stable in control perfusions (no kidney) with a disappearance half-life of greater than 250 min. The disappearance half-life in filtering kidneys was 52 +/- 3 min (COOH terminal) and 67 +/- 3 min (NH2-terminal). High-performance liquid chromatography of perfusate revealed a pattern similar to that seen in vivo with the NT being metabolized to NH2-terminal fragments. When the kidneys were rendered nonfiltering, NH2-terminal clearance was abolished, whereas COOH-terminal clearance was reduced by 75%. There was no release of NT peptidases into the perfusate. These data demonstrate that NT is metabolized directly by the kidney, predominantly by a filtration and reabsorption mechanism and with only a minor role for peritubular metabolism.

scholarly journals Metabolism of valine and 3-methyl-2-oxobutanoate by the isolated perfused rat kidney

1984 ◽  
Vol 224 (1) ◽  
pp. 109-116 ◽  
Author(s):  
R H Miller ◽  
A E Harper
Keyword(s):  
Amino Acids ◽  
High Activity ◽  
Rat Kidney ◽  
Linear Increase ◽  
Isolated Perfused Kidney ◽  
Isolated Perfused Rat Kidney ◽  
Acid Dehydrogenase ◽  
Perfused Rat Kidney ◽  
Branched Chain ◽  
Perfused Kidney

Metabolism of branched-chain amino and 2-oxo acids was studied in the isolated perfused kidney. Significant amounts of 2-oxo acids were released by perfused kidney with all concentrations of amino acids tested (0.1-1.0 mM each), despite the high activity of branched-chain 2-oxo acid dehydrogenase in kidney. As perfusate valine concentration was increased from 0.2 to 1.0 mM, [1-14C]valine transamination (2-oxo acid oxidized + released) increased roughly linearly; [1-14C]valine oxidation, however, increased exponentially. Increasing perfusate concentration of 3-methyl-2-oxo[1-14C]butanoate from 0 to 1.0 mM resulted in a linear increase in the rate of its oxidation and a rise in perfusate valine concentration; at the same time significant decreases occurred in perfusate isoleucine and leucine concentrations, with corresponding increases in rates of release of their respective 2-oxo acids. Comparison of rates of oxidation of [1-14C]valine and 3-methyl-2-oxo[1-14C]butanoate suggests that 2-oxo acid arising from [1-14C]valine transamination has freer access to the 2-oxo acid dehydrogenase than has the 2-oxo acid from the perfusate. The observations indicate that, when branched-chain amino and 2-oxo acids are present in perfusate at near-physiological concentrations, rates of transamination of the amino and 2-oxo acids by isolated perfused kidney are greater than rates of oxidation.

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