Removal and excretion of immunoreactive rat growth hormone by the isolated kidney

1981 ◽  
Vol 240 (4) ◽  
pp. F282-F287
Author(s):  
R. Rabkin ◽  
T. I. Gottheiner ◽  
V. S. Fang
Keyword(s):  
Growth Hormone ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Rat Kidney ◽  
Renal Circulation ◽  
Isolated Kidney ◽  
Perfused Rat Kidney ◽  
Rat Growth ◽  
Tubular Absorption ◽  
Organ Clearance

The renal uptake of immunoreactive rat growth hormone (rGH), molecular weight 21,500 daltons, was examined in the isolated perfused rat kidney to determine whether peritubular removal of a protein greater than 12,000 daltons occurs and to assess the functional characteristics of renal GH uptake. Organ clearance of rGH (OCGH) in control kidneys was 1,039 +/- 99 microliters/min and was unaffected by an excess of insulin but markedly depressed by col (10 degrees C( and KCN. Although glomerular filtration rate (GFR) did not differ significantly from OCGH in the control rats, we suspected that filtration could not account for all the rGH removed because of glomerular protein sieving. However, GFR was significantly less than OCGH with cold and KCN treatment, indicating the occurrence of peritubular removal. In nonfiltering kidneys, rGH removal exceeded that of [14C]inulin (P less than 0.05), demonstrating peritubular rGH removal. Tubular absorption of rGH was unaffected by insulin but markedly depressed by cold and KCN. We conclude that rGH is removed from the renal circulation mainly by the glomerular filtration-tubular absorptive pathway, but, in addition, as with smaller proteins, that peritubular removal occurs.

Low concentrations of ANP cause pressure-dependent natriuresis in the isolated kidney

1988 ◽  
Vol 255 (3) ◽  
pp. F391-F396 ◽  
Author(s):  
J. D. Firth ◽  
A. E. Raine ◽  
J. G. Ledingham
Keyword(s):  
Filtration Rate ◽  
Perfusion Pressure ◽  
Rat Kidney ◽  
Fractional Excretion ◽  
Renal Perfusion ◽  
Isolated Kidney ◽  
Renal Perfusion Pressure ◽  
Low Concentrations ◽  
Fractional Excretion Of Sodium ◽  
Perfused Rat Kidney

The effect of alteration in renal perfusion pressure on the response of the isolated perfused rat kidney to concentrations of alpha-human atrial natriuretic peptide (ANP) within the pathophysiological range has been examined. At a perfusion pressure of 90 mmHg ANP concentrations of 50, 200, and 1,000 pmol/l were without effect on any parameter tested. At a perfusion pressure of 130 mmHg 50 pmol/l ANP produced an increase of 3.13 +/- 0.68 mumol/min in sodium excretion (UNa V), compared with a fall of 0.33 +/- 1.04 mumol/min in controls (P less than 0.02); fractional excretion of sodium (FENa) rose by 1.45 +/- 0.36% vs. -0.12 +/- 0.47% (P less than 0.05); glomerular filtration rate (GFR) was unchanged. At 200 and 1,000 pmol/l larger changes in UNa V and FENa were seen; only at 1,000 pmol/l was a significant effect on GFR observed. In contrast, frusemide (furosemide) at concentrations of 10 and 100 mumol/l was natriuretic at both 90 and 130 mmHg, with lesser absolute but greater proportional changes being seen at the lower pressure. It was concluded 1) the response of the isolated kidney to ANP is critically dependent on perfusion pressure, 2) at elevated levels of perfusion pressure the isolated kidney can respond to levels of ANP within the upper physiological and pathophysiological range.

Renal catabolism of 125I-glicentin

1986 ◽  
Vol 250 (5) ◽  
pp. E545-E550 ◽  
Author(s):  
J. M. Lopez-Novoa ◽  
J. C. Santos ◽  
L. M. Villamediana ◽  
F. J. Garrote ◽  
L. Thim ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Distal Tubule ◽  
In Vivo Studies ◽  
Paired Data ◽  
Isolated Kidney ◽  
A Value ◽  
Organ Clearance

The renal catabolism of 125I-glicentin has been studied in vivo by the disappearance of this peptide from the plasma of bilaterally nephrectomized, ureteral-ligated, or normal rats and by using tubular microinfusion techniques. In addition the catabolism of glicentin by the isolated, perfused kidney has been studied. Results from in vivo studies demonstrated that half-disappearance time was lower in control (59.5 +/- 1.8 min) than in bilaterally nephrectomized rats (97.2 +/- 2.6 min), and this value was significantly higher than that of ureteral-ligated animals (83.2 +/- 1.1 min, P less than 0.005). Microinfusion experiments revealed that when 125I-glicentin was injected into the proximal tubule, no trichloroacetic-precipitable radioactivity was recovered in the urine, whereas most of inulin injected was recovered. By contrast most of the 125I-glicentin injected into the distal tubule was recovered in the urine. In isolated kidney experiments, organ clearance rate of 125I-glicentin averaged 0.88 +/- 0.10 ml/min, a value significantly higher than that of glomerular filtration rate (0.72 +/- 0.06 ml/min, P less than 0.005, paired data), and both parameters showed a close linear relationship (r = 0.90). Urinary clearance of glicentin was negligible. These results demonstrate that the kidney plays a major role in the catabolism of glicentin, mainly by glomerular filtration and tubular catabolism. The site of tubular catabolism appears to be the proximal tubule. Peritubular uptake was minimal.

Natriuretic and kaliuretic activities of guanylin and uroguanylin in the isolated perfused rat kidney

1998 ◽  
Vol 275 (2) ◽  
pp. F191-F197 ◽  
Author(s):  
Manasses C. Fonteles ◽  
Richard N. Greenberg ◽  
Helena S. A. Monteiro ◽  
Mark G. Currie ◽  
Leonard R. Forte
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Biological Effects ◽  
Rat Kidney ◽  
Second Messenger ◽  
Maximal Increase ◽  
Isolated Perfused Rat Kidney ◽  
Water Homeostasis ◽  
Perfused Rat Kidney

Guanylin and uroguanylin are novel peptides that activate membrane guanylate cyclases found in the kidney and intestine. We compared the effects of these peptides in the isolated perfused rat kidney. Both peptides are natriuretic and kaliuretic in this preparation. Uroguanylin (0.19–1.9 μM) increased glomerular filtration rate from 0.77 ± 0.07 to 1.34 ± 0.3 ml ⋅ g−1⋅ min−1at the highest concentration. A maximal increase in Na+excretion was achieved at 0.66 μM uroguanylin, with a reduction in fractional Na+reabsorption from 78.7 ± 1.7 to 58.8 ± 4.4%. The highest dose of uroguanylin increased kaliuresis by 50%. Osmolar clearance doubled at the highest concentration of uroguanylin tested ( P< 0.05). Guanylin also elicited a natriuresis and kaliuresis but appeared to be less potent than uroguanylin. The highest concentration of guanylin (1.3 μM) decreased fractional Na+reabsorption from 73.9 ± 2.4 to 64.5 ± 4.0%, but lower doses were ineffective. Guanylin stimulated urine K+excretion at the lowest concentration tested (0.33 μM) without any effect on Na+excretion. These peptides may influence salt and water homeostasis by biological effects in the kidney that are mediated by the intracellular second messenger, cGMP.

Handling of insulin by the isolated perfused rat kidney

1981 ◽  
Vol 240 (4) ◽  
pp. F288-F294 ◽  
Author(s):  
D. L. Maude ◽  
D. G. Handelsman ◽  
M. Babu ◽  
E. E. Gordon
Keyword(s):  
Molecular Weight ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Degradation Products ◽  
Rat Kidney ◽  
Kidney Tissue ◽  
Immunoreactive Insulin ◽  
Insulin Degradation ◽  
Organ Clearance

The organ clearance of insulin calculated from the rate of disappearance of immunoreactive insulin from the perfusate averages 0.76 ml.min-1.g kidneys wt-1, a value greater than the simultaneously measured glomerular filtration rate. Clearance does not fall when hormone concentration is as high as 7 X 10(-8) M (10,000 microunits/ml). Fifteen percent of the cleared insulin is excreted in the urine; the remainder is chemically modified and appears in the perfusate both as low molecular weight fragments and as high molecular weight species. In the process of clearing the hormone, kidney tissue accumulates both intact insulin and 125I-labeled insulin degradation products. the organ clearance of insulin is not curtailed when the glomerular filtration rate is sufficiently reduced (by lowering perfusate pressure) to cause urine flow to cease. Studies using hyperglycemic perfusates and kidneys taken from starving or streptozotocin-diabetic animals provided no evidence that the kidney plays a role in the regulation of plasma glucose by modulating the rate of insulin degradation.

Effects of growth hormone and IGF-I on renal function in rats with normal and reduced renal mass

1990 ◽  
Vol 259 (5) ◽  
pp. F747-F751 ◽  
Author(s):  
S. B. Miller ◽  
V. A. Hansen ◽  
M. R. Hammerman
Keyword(s):  
Growth Hormone ◽  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Renal Mass ◽  
Filtration Rate ◽  
Inulin Clearance ◽  
Mass Reduction ◽  
Contralateral Kidney ◽  
Igf I

To characterize actions of growth hormone (GH) and insulin-like growth factor ( (IGF-I) on renal function in rats with normal and reduced renal mass, we administered recombinant bovine growth hormone (bGH) or human IGF-I (hIGF-I) to normal rats or to rats that had undergone unilateral nephrectomy and two-thirds infarction of the contralateral kidney, and measured inulin and p-aminohippurate clearances over 10-17 days. Administration of either bGH (100-200 micrograms/day) or hIGF-I (200 micrograms/day) to rats with normal renal mass increased inulin and p-aminohippurate clearances compared with those measured in animals that received vehicle. Filtration fractions were not affected by either bGH or hIGF-I. Inulin clearance was decreased to approximately 17% of normal 1 day after reduction of renal mass in rats. Over the next 3 days insulin clearance increased significantly in rats with reduced renal mass that were administered vehicle. No further enhancement occurred during the next 7 days. Neither bGH nor hIGF-I affected inulin clearance in rats with reduced renal mass. We conclude that both GH and IGF-I enhance glomerular filtration rate when administered to rats with normal renal mass, but not when administered in the same quantities to rats in which renal functional mass is reduced. Glomerular filtration rate increases within 4 days of renal mass reduction independent of exogenous GH or IGF-I.

scholarly journals BTCI enhances guanylin-induced natriuresis and promotes renal glomerular and tubular effects

2008 ◽  
Vol 68 (1) ◽  
pp. 149-154 ◽  
Author(s):  
AF. Carvalho ◽  
MS. Santos-Neto ◽  
HSA. Monteiro ◽  
SM. Freitas ◽  
L. Morhy ◽  
...  
Keyword(s):  
Filtration Rate ◽  
Rat Kidney ◽  
Structural Features ◽  
Urine Flow ◽  
Renal Metabolism ◽  
Chymotrypsin Inhibitor ◽  
Electrolyte Homeostasis ◽  
Perfused Rat Kidney ◽  
First Time

Guanylin and uroguanylin are small cysteine-rich peptides involved in the regulation of fluid and electrolyte homeostasis through binding and activation of guanylyl cyclases signaling molecules expressed in intestine and kidney. Guanylin is less potent than uroguanylin as a natriuretic agent and is degraded in vitro by chymotrypsin due to unique structural features in the bioactive moiety of the peptide. Thus, the aim of this study was to verify whether or not guanylin is degraded by chymotrypsin-like proteases present in the kidney brush-border membranes. The isolated perfused rat kidney assay was used in this regard. Guanylin (0.2 µM) induced no changes in kidney function. However, when pretreated by the black-eyed pea trypsin and chymotrypsin inhibitor (BTCI - 1.0 µM; guanylin - 0.2 µM) it promoted increases in urine flow (deltaUF of 0.25 ± 0.09 mL.g-1/min, P < 0.05) and Na+ excretion (% delta ENa+ of 18.20 ± 2.17, P < 0.05). BTCI (1.0 µM) also increased %ENa+ (from 22.8 ± 1.30 to 34.4 ± 3.48, P < 0.05, 90 minutes). Furthermore, BTCI (3.0 µM) induced increases in glomerular filtration rate (GFR; from 0.96 ± 0.02 to 1.28 0.02 mL.g-1/min, P < 0.05, 60 minutes). The present paper strongly suggests that chymotrypsin-like proteases play a role in renal metabolism of guanylin and describes for the first time renal effects induced by a member of the Bowman-Birk family of protease inhibitors.

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