25-hydroxyvitamin D3 metabolism by isolated perfused rat kidney

1980 ◽  
Vol 239 (1) ◽  
pp. E12-E20 ◽  
Author(s):  
A. M. Rosenthal ◽  
G. Jones ◽  
S. W. Kooh ◽  
D. Fraser
Keyword(s):  
Vitamin D ◽  
Rat Kidney ◽  
Adult Rats ◽  
Renal Metabolism ◽  
Dihydroxyvitamin D3 ◽  
Metabolic Pattern ◽  
End Products ◽  
Perfused Rat Kidney ◽  
Semisynthetic Media ◽  
High Yields

Kidneys of adult rats were removed and perfused with semisynthetic media with the object of elucidating the separate actions of factors implicated as modulators of renal metabolism of 25-hydroxyvitamin D3 (25(OH)D3). During a 3-h perfusion with 3[H]25(OH)D3, the kidney produced high yields of 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) or 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) depending on whether the rat had previously been, respectively, normocalcemic, normophosphatemic, vitamin D-replete or hypocalcemic, hypophosphatemic, vitamin D-deplete. With longer perfusion (up to 12 h), kidneys from normocalcemic, normophosphatemic, vitamin D-replete rats mainly produced 24,25(OH)2D3 but also amounts of 1,25(OH)2D3. This pattern was unaltered by reducing Ca or Pi concentrations of perfusate or by adding parathyroid hormone. Kidneys of hypocalcemic, hypophosphatemic, vitamin D-deplete rats perfused with low Ca, low Pi medium for 12 h at first produced 1,25(OH)2D3 exclusively. However, 24,25(OH)2D3 appeared after 4 h and accumulated thereafter, whereas 1,25(OH)2D3 synthesis ceased after 7 h, a metabolic pattern unaffected by the concentration of substrate or end products in the perfusate or by addition of cyclic AMP. The model shows promise for studying regulation of 25(OH)D3 metabolism by the kidney.

Inhibition of 25-hydroxyvitamin D3-1-hydroxylase by chronic metabolic acidosis

1982 ◽  
Vol 243 (4) ◽  
pp. E265-E271
Author(s):  
G. S. Reddy ◽  
G. Jones ◽  
S. W. Kooh ◽  
D. Fraser
Keyword(s):  
Vitamin D ◽  
Metabolic Acidosis ◽  
Rat Kidney ◽  
Ion Concentration ◽  
Hydroxylase Activity ◽  
Renal Metabolism ◽  
Dihydroxyvitamin D3 ◽  
Hydrogen Ion Concentration ◽  
Chronic Metabolic Acidosis ◽  
Negative Linear Correlation

Chronic metabolic acidosis had been shown to influence the renal metabolism of 25-hydroxyvitamin D3. Using the isolated perfused rat kidney model, we evaluated the rates of synthesis of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] in vitamin D-depleted [D(-)] and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] in vitamin D-replete [D(+)] rats. Metabolic acidosis was induced in both groups of rats by feeding aqueous ammonium chloride for 9 days. Kidneys isolated from D(-) acidotic rats (mean pH, 7.11) exhibited a decreased rate of 1,25(OH)2D3 synthesis (0.79 +/- 0.17 pmol produce . h-1 . g kidney-1) when compared with that (1.27 +/- 0.09) of D(-) nonacidotic (mean pH, 7.33) rats. There was a significant negative linear correlation between the rate of synthesis of 1,25(OH)2D3 and the hydrogen ion concentration of the animal (r = 0.79, P less than 0.005). The rate of synthesis of 24,25(OH)2D3 by the kidneys from D(+) acidotic (mean pH, 7.06) and nonacidotic (mean pH, 7.39) rats did not differ (0.81 +/- 0.21 vs. 0.60 +/- 0.12 pmol product . h-1 . g kidney-1). It is concluded that chronic acidosis suppressed 1-hydroxylase activity, but does not suppress 24-hydroxylase activity.

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.

Intestinal phosphate absorption: influence of vitamin D and non-vitamin D factors

1986 ◽  
Vol 250 (3) ◽  
pp. G369-G373 ◽  
Author(s):  
D. B. Lee ◽  
M. W. Walling ◽  
N. Brautbar
Keyword(s):  
Vitamin D ◽  
Adult Rats ◽  
Dihydroxyvitamin D3 ◽  
Treatment Groups ◽  
Transport Of Inorganic Phosphate ◽  
P Flux ◽  
Intestinal Phosphate Absorption ◽  
P Absorption

The transport of inorganic phosphate (P) was measured in the absence of electrochemical gradients across rat jejunum in vitro. Active P absorption was demonstrated in young, vitamin D-deficient (-D) rats, whereas active P secretion was found in normal, non-vitamin D-deficient adult rats, suggesting regulation of intestinal P transport by age-dependent but vitamin D-independent mechanisms. 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] stimulated mucosal-to-serosal P flux (Jm----s) without affecting serosal-to-mucosal P flux (Js----m), causing further increases in net P absorption (Jnet) in -D rats and reduction in net P secretion in normal adult rats, confirming a previously described role of this hormone on P absorption. We then examined the effect of increasing extracellular (buffer) P concentration [P] on this 1,25(OH)2D3-stimulated active P absorption in jejunum from -D rats. At [P] of 0.024, 0.24, and 2.4 mM, 1,25(OH)2D3 consistently stimulated Jm----s without affecting Js----m, causing an increment in Jnet. At 7.5 mM [P], however, this Jm----s stimulatory effect of 1,25(OH)2D3 was no longer observed. Moreover, at this [P] the Js----m exceeded Jm----s in both -D and 1,25(OH)2D3-repleted rats, converting the active P absorption into active P secretion in both treatment groups. These observations suggest the participation of local mechanisms, such as the ambient [P] of the transporting enterocytes, in the regulation of intestinal P absorption. Finally, the influence of dietary P deprivation on P absorption was studied in -D rats, with or without either vitamin D3 or 1,25(OH)2D3 repletion.(ABSTRACT TRUNCATED AT 250 WORDS)

Excretion and metabolism of dopa and dopamine by isolated perfused rat kidney

1984 ◽  
Vol 247 (3) ◽  
pp. E285-E290 ◽  
Author(s):  
H. Suzuki ◽  
H. Nakane ◽  
M. Kawamura ◽  
M. Yoshizawa ◽  
E. Takeshita ◽  
...  
Keyword(s):  
Rat Kidney ◽  
Dopa Decarboxylase ◽  
Physiological Concentration ◽  
Renal Metabolism ◽  
Isolated Perfused Rat Kidney ◽  
Perfused Rat Kidney ◽  
Urinary Dopamine ◽  
Physiological Values ◽  
Dopa Concentration ◽  
Renal Dopamine

The renal metabolism and handling of dopa and dopamine were studied with the use of the isolated perfused rat kidney to elucidate the source of urinary dopamine. Dopa added to the perfusate was rapidly metabolized, and a significant amount of urinary dopamine excretion was observed, whereas dopa was not detected in the urine. When the perfusate dopa concentration was near the plasma dopa concentration in normal rats, urinary dopamine excretion was comparable with physiological values. Carbidopa, a dopa decarboxylase blocker, added to the perfusate markedly reduced the urinary excretion of dopamine. When the physiological concentration of dopamine was added to the medium, the perfusate dopamine rapidly decreased and urinary dopamine excretion was much less than that seen in normal rats. In studies with nonfiltering kidneys, a marked decrease of dopa and slight increase of dopamine in the perfusate were observed. It is suggested that the process of glomerular filtration and tubular reuptake of dopa is not essential for renal dopamine formation. These data indicate that urinary free dopamine is mainly derived from plasma dopa, which is converted by dopa decarboxylase in the kidney.

Aldosterone metabolism in isolated perfused rat kidney.

1978 ◽  
Vol 234 (5) ◽  
pp. E472
Author(s):  
H Nakane ◽  
Y Nakane ◽  
G Reach ◽  
P Corvol ◽  
J Menard
Keyword(s):  
Urinary Excretion ◽  
Perfusion Pressure ◽  
Rat Kidney ◽  
Urine Volume ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Renal Metabolism ◽  
Isolated Perfused Rat Kidney ◽  
Perfused Rat Kidney ◽  
Acid Labile

The renal metabolism and handling of [1,2-3H]aldosterone ([3H]A) was studied using isolated perfused rat kidney under different perfusion conditions. The metabolite production rate (MPR) and the urinary excretion of [3H]A together with its radiometabolites (UV/P3H) were studied. Among the formed metabolites, no acid-labile conjugate of aldosterone (ALC) was detected. The MPR was not altered in studies using nonfiltering kidney, a result that suggests that the majority of metabolites were formed without requirement of the process of glomerular filtration and tubular uptake of the hormone. High perfusion pressure (high PP) resulted in a striking increase in whole metabolic clearance rate of aldosterone (MCR[3H]A) due mostly to an enhanced urinary excretion of intact aldosterone and, to a lesser degree, to a significant increase in MPR. Factors determining the excretion rate of [3H]A and its metabolites were than investigated under administration of diuretics. Mannitol (44 mM) induced a marked increase in urine volume (UV) accompanied by a significant UV/P3H increase. Meanwhile, 0.1 mM furosemide resulted in an increase only in UV, but not in UV/P3H. These results revealed the UV dependence of aldosterone excretion in certain diuretic conditions.

Isolation and identification of seven metabolites of 25-hydroxydihydrotachysterol3 formed in the isolated perfused rat kidney: a model for the study of side-chain metabolism of vitamin D

Biochemistry ◽  
1988 ◽  
Vol 27 (18) ◽  
pp. 7070-7079 ◽  
Author(s):  
Glenville Jones ◽  
Nancy Edwards ◽  
Dorothy Vriezen ◽  
Caroline Porteous ◽  
David J. H. Trafford ◽  
...  
Keyword(s):  
Vitamin D ◽  
Rat Kidney ◽  
Side Chain ◽  
Isolation And Identification ◽  
Isolated Perfused Rat Kidney ◽  
Perfused Rat Kidney

Renal Metabolism of Paracetamol: Studies in the Isolated Perfused Rat Kidney

1980 ◽  
Vol 58 (5) ◽  
pp. 379-384 ◽  
Author(s):  
Sandra Hart ◽  
I. Calder ◽  
B. Ross ◽  
J. Tange
Keyword(s):  
Oxidative Metabolism ◽  
Physiological Function ◽  
Rat Kidney ◽  
Mercapturic Acid ◽  
Renal Metabolism ◽  
Isolated Perfused Rat Kidney ◽  
Perfused Rat Kidney

1. The metabolism of [3H]paracetamol has been studied in the perfused rat kidney. Seventy-four per cent of filtered paracetamol was reabsorbed. Paracetamol appeared in the urine; 90%was unaltered but 10%appeared as metabolites: the glucuronide, sulphate, mercapturic acid and cysteine conjugates. 2. At concentrations of paracetamol of 1–3 mmol/l no impairment of renal physiological function was observed. 3. The presence of the mercapturic acid and cysteine conjugates in the urine demonstrates the capacity of the kidney for oxidative metabolism of paracetamol and hence the formation of potentially toxic intermediates.

Intestinal and metabolic effect of 1,25-dihydroxyvitamin D3 in normal adult rat

1981 ◽  
Vol 240 (1) ◽  
pp. G90-G96 ◽  
Author(s):  
D. B. Lee ◽  
M. M. Walling ◽  
B. S. Levine ◽  
U. Gafter ◽  
V. Silis ◽  
...  
Keyword(s):  
Vitamin D ◽  
Phosphate Uptake ◽  
Phosphate Transport ◽  
Biological Action ◽  
Normal Adult ◽  
Adult Rats ◽  
Dihydroxyvitamin D3 ◽  
45Ca Uptake ◽  
Adult Rat ◽  
1,25 Dihydroxyvitamin D3

We examined the effect of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on intestinal 45Ca and [32P]phosphate uptake in normal and mineral- and vitamin D-replete adult rats. The results indicate that 45Ca uptake by adult rat duodenum was stimulated by "physiological" doses of 1,25(OH)2D3. With increasing dosage of 1,25(OH)2D3, 45Ca uptake also became stimulated first in the colon and then in the jejunum and ileum. The increase in duodenal and jejunal 45Ca uptake was paralleled by an increase in [32P]phosphate uptake, but this parallelism was not always seen in the ileum and was never observed in the colon. The dissociated calcium and phosphate transport response to 1,25(OH)2D3 stimulation in the colon was further confirmed by the measurement of transmural fluxes using a modified Ussing technique. These responses to 1,25(OH)2D3 are similar to those observed in younger vitamin D-deficient rats. However, supraphysiological doses of 1,25(OH)2D3 caused weight loss in normal adult rats, whereas the same metabolite, even when given in large doses, led to weight gain in vitamin D-deficient rats. We propose the normal adult rat as an additional model for evaluating the biological action of 1,25(OH)2D3.

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