Sulfation in isolated kidney tubule fragments of rats dependence of inorganic sulfate (original) (raw)
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Sulfation in isolated enterocytes of guinea pig: Dependence on inorganic sulfate
Biochemical Pharmacology, 1984
Isolated intestinal epithelial cells of the guinea-pig were used to study uptake and metabolism of inorganic sulfate in the jejunum (proximal cells) and ileum (distal cells). Proximal enterocytes accumulated sulfate 1.5-fold and distal enterocytes 3.1-fold. Accumulation was almost linearly related to substrate concentrations up to 5 mM. In proximal cells, despite their lower intracellular sulfate levels, sulfate incorporation into acid-precipitable material and sulfate conjugation of I-naphthol were faster than in distal cells. Formation of 1-naphthyl sulfate increased with extracellular sulfate concentrations up to 1 and 3 mM sulfate in distal and proximal enterocytes, respectively. The data suggest that the extent of intestinal sulfation of phenolic compounds may be enhanced by oral administration of sulfate.
Journal of Pharmacology and Experimental Therapeutics
The renal transport and fractional reabsorption of inorganic sulfate is altered under conditions of sulfate deficiency or excess. The objective of this study was to examine the cellular mechanisms of adaptation of renal sodium/sulfate cotransport after varying dietary intakes of a sulfur containing amino acid, methionine. Female Lewis rats were divided into four groups and fed diets containing various concentrations of methionine (0, 0.3, 0.82 and 2.46%) for 8 days. Urinary excretion rates and renal clearance of sulfate were significantly decreased in the animals fed a 0% methionine diet or a 0.3% methionine diet, and significantly increased in the animals fed a 2.46% methio-nine diet when evaluated on days 4 and 7. Serum sulfate concentrations were unchanged by diet treatment in all animals. The fractional reabsorption of sulfate was significantly increased in the animals fed the 0% methionine diet and the 0.3% methionine diets, and decreased in the animals fed the 2.46% methionine diet. Increased mRNA and protein levels for the sodium/sulfate transporter (NaSi-1) were found in the kidney cortex following treatment with the 0 and 0.3% methionine diet groups. Sulfate homeostasis by renal reabsorption is maintained by an up-regulation of steady state levels of NaSi-1 mRNA and protein when the diet is low in methionine.
AJP: Regulatory, Integrative and Comparative Physiology, 2005
Electrospray tandem mass spectrometry was used to determine steady-state serum and urinary inorganic sulfate and sulfate ester kinetic profiles of nine normal men after intravenous injection of the stable isotope sodium [ 34 S]sulfate. Sulfate ester appearance was traced by eliminating inorganic sulfate from samples, followed by hydrolysis of sulfate esters to inorganic sulfate for analysis. Whole body inorganic sulfate turnover in steady state was calculated using standard tracer techniques. Rate of appearance and disappearance of inorganic sulfate was 841 Ϯ 49 mol/h. Average urinary inorganic sulfate excretion was 609 Ϯ 41 mol/h, and the whole body sulfation rate (total rate of disappearance minus rate of urinary excretion) was 232 Ϯ 36 mol/h. Tracer-labeled sulfate esters appeared in serum and urine within 1 h of tracer injection. The kinetics of inorganic sulfate and sulfate esters were linked by means of a compartmental model. The appearance and excretion of sulfate esters accounted for ϳ 50% of the total sulfation rate. These results indicate that human whole body sulfation accounts for ϳ 27% of inorganic sulfate turnover and that extracellular inorganic sulfate is an important pool for intracellular sulfation. A substantial fraction of newly synthesized sulfate esters promptly enters the extracellular space for excretion in the urine.
Transport, Binding, and Futile Cycling of Sulfate Conjugates in Liver
Drug Metabolism and Pharmacokinetics, 1993
Sulfate conjugates are an important class of polar compounds which are highly ionized at physiological pH. The liver is the most important sulfation organ for most substrates. When formation and processing of sulfate conjugates are viewed as distributed-in-space phenomena, that drug and sulfate conjugate cell entry and removal occur along the direction of flow such that a concentration gradient is created from the inlet to the outlet of the liver, the differential handling of the formed vs. preformed sulfate conjugate becomes apparent. From single-pass prograde (P, entry via portal vein) and retrograde (R, entry via hepatic vein) single pass perfusion studies, formation of sulfate conjugates from acetaminophen (1), harmol (2), gentisamide (3), salicylamide (4) and 4-methylumbelliferone (4MU) (5) was found to occur in the periportal (zone 1) of the rat liver. The anterior sulfation activities modulate the substrate flux and metabolic rates with downstream enzymes. Most sulfate conjugates undergo biliary excretion. However, 4-methylumbelliferyl sulfate (4MUS) suffers desulfation mediated via evenly distributed arylsulfatases (6,7) to refurnish the aglycone .
The Biochemical journal, 1978
1. The metabolism of inorganic [(35)S]sulphate (Na(2) (35)SO(4)) was studied in the isolated perfused rat liver at three initial concentrations of inorganic sulphate in the perfusion medium (0, 0.65 and 1.30mm), in relation to sulphation and glucuronidation of a phenolic drug, harmol (7-hydroxy-1-methyl-9H-pyrido[3,4-b]indole). 2. [(35)S]Sulphate rapidly equilibrated with endogenous sulphate in the liver. It was excreted in bile and reached, at the lowest concentration in the perfusion medium, concentrations in bile that were much higher than those in the perfusion medium; at the higher sulphate concentrations, these concentrations were equal. The physiological concentration of inorganic sulphate in the liver, available for sulphation of drugs, is similar to the plasma concentration. 3. At zero initial inorganic sulphate in the perfusion medium, the rate of sulphation was very low and harmol was mainly glucuronidated. At 0.65mm-sulphate glucuronidation was much decreased and conside...
Localization of the sulfate/anion exchanger in the rat liver
American Journal of Physiology-Gastrointestinal and Liver Physiology, 2005
Although the sulfate/anion transporter (sat-1; SLC26A1) was isolated from a rat liver cDNA library by expression cloning, localization of sat-1 within the liver and its contribution to the transport of sulfate and organo sulfates have remained unresolved. In situ hybridization and immunohistochemical studies were undertaken to demonstrate the localization of sat-1 in liver tissue. RT-PCR studies on isolated hepatocytes and liver endothelial and stellate cells in culture were performed to test for the presence of sat-1 in these cells. In sulfate uptake and efflux experiments, the substrate specificity of sat-1 was evaluated. Sat-1 mRNA was found in hepatocytes and endothelial cells. Sat-1 protein was localized in sinusoidal membranes and along the borders of hepatocytes. The canalicular region and bile capillaries were not stained. Sulfate uptake was only slightly affected by sulfamoyl diuretics or organo sulfates. Sulfate efflux from sat-1-expressing oocytes was enhanced in the pres...
Transport, binding, and metabolism of sulfate conjugates in the liver
Chemico-Biological Interactions, 1994
Sulfate conjugates are a heterogeneous class of polar, anionic metabolites that result from the conjugation of endogenous and exogenous compounds. Sulfate conjugates exhibit a high degree of binding to albumin, the extent of which usually exceeds those of their parent compounds. Preponderant direct and indirect evidence suggests that sulfation activity is slightly higher in the periportal than in the perivenous (centrilobular) region of the liver, but recent immunohistochemical studies imply that specific isoforms of the sulfotransferases may also be preferentially localized in the perivenous region. Entry of sulfate conjugates into the liver cell is poor unless discrete carriers are present. Although known transport carriers exist for the sulfated bile acids, the specificity of the carriers for drug sulfate conjugates is presently unknown. The removal of sulfates is usually by way of biliary excretion while, on occasion, sulfates can be desulfated and participate in futile cycling with their parent compounds. The binding, transport, and hepatic elimination of various drug sulfate conjugates are examined. Non-recirculating studies carried out in the perfused rat liver with the multiple indicator dilution technique under varying input sulfate conjugate concentrations have provided essential information on the effects of vascular (red blood cells and plasma protein) binding on transport and removal of the conjugates. These studies clearly demonstrate the need to study protein binding, transmembrane transfer characteristics across the liver basolateral (sinusoidal) and canalicular membranes, and enzyme zonation in a distributed-in-space fashion in order to properly define the handling of sulfate conjugates in the liver.
Renal sulfate reabsorption in healthy individuals and renal transplant recipients
Physiological reports, 2018
Inorganic sulfate is essential for normal cellular function and its homeostasis is primarily regulated in the kidneys. However, little is known about renal sulfate handling in humans and particularly in populations with impaired kidney function such as renal transplant recipients (RTR). Hence, we aimed to assess sulfate reabsorption in kidney donors and RTR. Plasma and urinary sulfate were determined in 671 RTR and in 251 kidney donors. Tubular sulfate reabsorption (TSR) was defined as filtered load minus sulfate excretion and fractional sulfate reabsorption (FSR) was defined as 1-fractional excretion. Linear regression analyses were employed to explore associations of FSR with baseline parameters and to identify the determinants of FSR in RTR. Compared to kidney donors, RTR had significantly lower TSR (15.2 [11.2-19.5] vs. 20.3 [16.7-26.3] μmol/min), and lower FSR (0.56 [0.48-0.64] vs. 0.64 [0.57-0.69]) (all P < 0.001). Kidney donation reduced both TSR and FSR by circa 50% and 2...
Sulfate transport in rabbit ileum: Characterization of the serosal border anion exchange process
The Journal of Membrane Biology, 1981
The preceding paper [30] shows that transepithelial ileal SO4 transport involves Na-dependent uptake across the ileal brush border, and Cl-dependent efflux across the serosal border. The present study examines more closely the serosal efflux process. Transepithelial mucosa (m)-to-serosa (s) and sto-m fluxes (Jms, Jsm) across rabbit ileal mucosa were determined under short-circuit conditions. SO4 was present at 0,22 mM. In standard C1, HCO3 Ringer's, jso4 was 81.3 +5.3 (1SE) and jso4 was 2.5_+0.2 nmol cm-2hr-l(n=20). Serosal addition of 4-acetamido-4'-isothiocyanostilbene-22'-disulfonate (SITS), 44'-diisothiocyanostilbene-22'-disulfonate (DIDS) or 1-anilino-8-naphthalene-sulfonate (ANS) inhibited SO4 transport, SITS being the most potent. Several other inhibitors of anion exchange in erythrocytes and other cells had no effect on ileal SO4 fluxes. In contrast to its effect on SO4 transport, SITS (500 gM) did not detectably alter C1 transport.