Cystine and lysine reabsorption in the isolated perfused rat kidney

1989 ◽  
Vol 256 (5) ◽  
pp. F901-F908
Author(s):  
K. A. Roby ◽  
S. Segal

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.

1995 ◽  
Vol 269 (4) ◽  
pp. C917-C922 ◽  
Author(s):  
K. Yoshioka ◽  
J. W. Fisher

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.


1992 ◽  
Vol 263 (2) ◽  
pp. R273-R278
Author(s):  
M. R. Lebowitz ◽  
A. M. Moses ◽  
S. J. Scheinman

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)


1957 ◽  
Vol 41 (1) ◽  
pp. 49-61 ◽  
Author(s):  
Ingrith J. Deyrup

Rat kidney cortical slices, during incubation in vitro, lose previously accumulated radiosulfur when exposed to conditions (e.g. addition to the medium of metabolic inhibitors) which normally depress the uptake of S35. The extent of this loss is not affected significantly by the presence of phlorhizin, an agent which enhances markedly radiosulfate accumulation. On the other hand, when tissues are chilled to 1°C., loss is slight or negligible even in the presence of metabolic inhibitors. These data, and observations on the effect of pre-incubation of kidney slices in S35-free media before the addition of radiosulfate, have been interpreted as evidence that S35 accumulation in vitro may be resolved into at least two processes, namely (a) entrance of the isotope-labelled anion into the cells, by diffusion and/or active transport, and (b) complexing of S35 (in ionic or other form) with an intracellular component. The postulated complex is stabilized, perhaps through inactivation of a specific enzyme, by chilling the tissue to 1°C. Possible relationships are discussed among the observations noted above, sulfur metabolism in general, and aspects of the known in vivo transport mechanism for sulfate ion; i.e., renal tubular reabsorption.


1985 ◽  
Vol 229 (2) ◽  
pp. 545-549 ◽  
Author(s):  
M Lowry ◽  
D E Hall ◽  
J T Brosnan

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.


Toxicon ◽  
2019 ◽  
Vol 165 ◽  
pp. 40-46
Author(s):  
Mauren Villalta ◽  
Tiago Lima Sampaio ◽  
Ramon Róseo Paula Pessoa Bezerra de Menezes ◽  
Dânya Bandeira Lima ◽  
Antônio Rafael Coelho Jorge ◽  
...  

1985 ◽  
Vol 249 (5) ◽  
pp. E494-E497 ◽  
Author(s):  
R. M. Rosa ◽  
P. Silva ◽  
J. S. Stoff ◽  
F. H. Epstein

Vasoactive intestinal peptide, a polypeptide neurotransmitter, stimulates salt secretion by the mammalian intestine and the rectal gland of the dogfish shark. Because of the recent identification of vasoactive intestinal peptide in renal nerves, the present study was undertaken to investigate its effects on the isolated perfused rat kidney. The addition of vasoactive intestinal peptide to the recirculating perfusate produced a significant increase in urine volume, fractional excretion of sodium, chloride, and potassium, as well as osmolar clearance when compared with control kidneys. These changes associated with addition of vasoactive intestinal peptide occurred without any significant changes in perfusion flow, renal vascular resistance, or inulin clearance. These experiments strongly suggest an action of vasoactive intestinal peptide on renal tubular reabsorption.


2009 ◽  
Vol 53 (7) ◽  
pp. 2857-2864 ◽  
Author(s):  
Zheng Ma ◽  
Jiping Wang ◽  
Roger L. Nation ◽  
Jian Li ◽  
John D. Turnidge ◽  
...  

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.


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