Sulfation in isolated enterocytes of guinea pig: Dependence on inorganic sulfate (original) (raw)
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Chemico-Biological Interactions, 1994
Sulfation requires 3'-phosphoadenosine 5'-phosphosulfate (PAPS) as the sulfate donor. In the search for methods to inhibit sulfation reactions via impairment of PAPS synthesis, two experimental conditions have been tested in rats. A low-sulfur diet, which does not deplete hepatic glutathione, reduced inorganic sulfate but not PAPS levels in the liver and moderately decreased sulfation of acetaminophen. Administration of molybdate, which is an alternative substrate for intestinal and renal sulfate transport as well as for ATP-sulfurylase, depleted both sulfate and PAPS in liver and markedly inhibited sulfation of acetaminophen. Therefore, administration of molybdate may be used as an experimental tool to study the role of sulfation in the fate and effect of xenobiotics.
The Journal of Membrane Biology, 1981
port rates greater than 1.4 gEq hr 1 cm -2, neither addition of SO4 to the SO4-free medium nor addition of SITS to SO4-containing medium altered short-circuit current. The results suggest that (1) ileal SO4 absorption consists of Na-coupled influx (symport) across the brush border and Cl-coupled efflux (antiport) across the basolateral membrane; (2) the overall process is electrically neutral; (3) the medium-to-cell C1 concentration difference may provide part of the driving force for net SO~ absorption; and (4) since agents affecting Cl fluxes (both absorptive and secretory) have little effect on SO4 fluxes, the mechanisms for their transcellular transports are under separate regulation.
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...
Studies on Intestinal Absorption of Sulpiride (3): Intestinal Absorption of Sulpiride in Rats
Biological and Pharmaceutical Bulletin, 2004
The aim of this study was to investigate whether the concomitant administration of the substrates or inhibitors of PEPT1, OCTN1, OCTN2, and P-glycoprotein affects the intestinal absorption of sulpiride in rats. The absorption of sulpiride from rat intestine was decreased by the substrates or inhibitors of PEPT1, OCTN1, and OCTN2. On the other hand, the absorption was increased by the substrates of P-glycoprotein. The effects of these concomitantly administered drugs on the pharmacokinetic behavior of sulpiride after oral administration in rats were investigated. Peak concentration (C max) and area under the plasma concentration-time curve (AUC 0-8 h) of sulpiride were decreased by the concomitant administration of the substrates or inhibitors of PEPT1, OCTN1, and OCTN2. However, the same parameters were significantly increased by the concomitant administration of the substrates of P-glycoprotein. The present results suggest the possibility of drug-drug interaction during the absorption process in the small intestine due to the coadministration of sulpiride and these agents. These findings provide important information for preventing adverse effects and for ensuring the effectiveness of sulpiride and concomitantly administered drugs.
Sulfation in isolated kidney tubule fragments of rats dependence of inorganic sulfate
Biochemical Pharmacology, 1985
Uptake and conjugation of sulfate was studied in isolated kidney tubule fragments of rats: Sulfate is rapidly taken up, and maximal cellular concentrations are attained after 5-10 min; intracellular steady-state levels depend on the sulfate concentrations of the medium and attain a maximal value at 2 mM. At 1 mM sulfate in the medium the ratio of intracellular/extracellular concentrations of the inorganic anion amount to about 0.25. Formation of 7-hydroxycoumarin sulfate increases almost linearly up to an extracellular sulfate concentration of 500 .uM. Thereafter, rates of sulfation increase more slowly and maximal sulfation rates are attained at 2 mM sulfate.
Intestinal Effects of Sulfate in Drinking Water on Normal Human Subjects
Digestive Diseases and Sciences, 1997
Uncontrolled observations implicate sulfate indrinking water at concentrations exceeding 500-700mg/liter as a cause of diarrhea, but controlled studieshave not been reported. We conducted a controlled study in normal adults to determine the effectof various drinking water sodium sulfate concentrationson bowel function. Ten healthy subjects were given aconstant diet and fluid intake. Fluid consisted of 36 ml/kg/day of drinking water of
Metabolism of dietary sulphate: absorption and excretion in humans
Gut, 1991
Dietary sulphate may affect colonic pathophysiology because sulphate availability determines in part the activity of sulphate reducing bacteria in the bowel. The main product of sulphate reducing bacterial oxidative metabolism, hydrogen sulphide, is potentially toxic. Although it is generally believed that the
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.
Nutritional Aspects of Dissimilatory Sulfate Reduction in the Human Large Intestine
Current Microbiology, 1997
In contrast to other anaerobic ecosystems, such as marine and estuarine sediments, there is a lack of information on the nutritional requirements of human gut sulfate-reducing bacteria (SRB). Various substrates stimulated sulfate reduction in mixed culture, including short-chain fatty acids and other organic acids, alcohols, and amino acids (but not sugars or aromatic compounds). However, the use of sodium molybdate as a specific inhibitor of sulfate reduction caused an accumulation of ethanol and malonate only, and reduced the rate of utilization of lactate. This indicates the importance of these electron donors for sulfate reduction. Since ethanol and lactate are primarily utilized by members of the Desulfovibrio genus, the results suggest a physiologically important role for this group.
Journal of Animal Science, 2010
Two experiments investigated the impact of dietary inorganic S on growth performance, intestinal inflammation, fecal composition, and the presence of sulfate-reducing bacteria (SRB). In Exp. 1, individually housed pigs (n = 42; 13.8 kg) were fed diets containing 2,300 or 2,100 mg/kg of S for 24 d. Decreasing dietary S had no effect on ADG, ADFI, or G:F. In Exp. 2, pigs (n = 64; 13.3 kg) were fed diets containing 0, 0.625, 1.25, 2.5, or 5.0% CaSO 4 , thereby increasing dietary S from 2,900 to 12,100 mg/kg. Two additional diets were fed to confirm the lack of an impact due to feeding low dietary S on pig performance and to determine if the increased Ca and P content in the diets containing CaSO 4 had an impact on growth performance. Pigs were fed for 35 d. Ileal tissue, ileal mucosa, and colon tissue were harvested from pigs fed the 0 and 5% CaSO 4 diets (low-S and highS , respectively) to determine the impact of dietary S on inflammation-related mRNA, activity of mucosal alkaline phosphatase and sucrase, and pathways of inflammatory activation. Real-time PCR was used to quantify SRB in ileal and colon digesta samples and feces. Fecal pH, sulfide, and ammonia concentrations were also determined. There was no impact on growth performance in pigs fed the diet reduced in dietary S or by the increase of dietary Ca and P. Increasing dietary S from 2,900 to 12,100 mg/kg had a linear (P < 0.01) effect on ADG and a cubic effect (P < 0.05) on ADFI and G:F. Real-time reverse-transcription PCR analysis revealed that pigs fed highS increased (P < 0.05) the relative abundance of intracellular adhesion molecule-1, tumor necrosis factor-α, and suppressor of cytokine signaling-3 mRNA, and tended (P = 0.09) to increase the relative abundance of IL-6 mRNA in ileal tissue. Likewise, pigs fed highS had reduced (P < 0.05) abundance of nuclear factor of κ light polypeptide gene enhancer in B-cells inhibitor-α and increased (P < 0.05) phospho-p44/p42 mitogen-activated protein kinase in ileal tissue, but there was no effect of dietary S on mucosal alkaline phosphatase or sucrase activity. Pigs fed the highS diet had decreased (P < 0.05) total bacteria in ileal digesta, but increased (P < 0.05) prevalence of SRB in colon contents. Fecal sulfide was increased (P < 0.05) and fecal pH was deceased (P < 0.05) in pigs fed highS. The data indicate that growing pigs can tolerate relatively high amounts of dietary inorganic S, but high dietary S content alters inflammatory mediators and intestinal bacteria.