Unique mechanism of inhibition of Na<sup>+</sup>-amino acid cotransport during chronic ileal inflammation

Sundaram, Uma; Wisel, Sheik; Fromkes, John J.

doi:10.1152/ajpgi.1998.275.3.g483

Cited by 38 publications

(53 citation statements)

References 15 publications

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“…BBM vesicles (BBMV) from rabbit intestinal villus cells were prepared by CaCl 2 precipitation, and differential centrifugation as previously reported (23,24). BBMV were resuspended in a medium appropriate to each experiment.…”

Section: Drug Treatmentmentioning

confidence: 99%

“…Uptake studies were performed in villus cells by the rapid filtration technique as previously described (23,24). Villus cells (100 mg wet wt) were washed and resuspended in HEPES buffer containing (in mM) 1.25 3-O-methyl-D-glucose (3-OMG) or L-alanine, 4.5 KC1, 1.2 KH2PO4, 1.0 MgSO4, 1.25 CaC12, 20 HEPES, and either 130 NaCl or choline chloride and were gassed with 100% O2 (pH 7.4 at 37°C).…”

Section: Drug Treatmentmentioning

confidence: 99%

“…Vesicle uptake studies were performed by the rapid-filtration technique as previously described (23,24). In brief, 5 l of BBMV resuspended in 100 mM choline chloride, 0.10 mM MgSO 4, 50 mM HEPES-Tris (pH 7.5), 50 mM mannitol, and 75 mM KCl were incubated in 95 l of reaction medium that contained 50 mM HEPES-Tris buffer (pH 7.5), 0.1 mM 3-OMG or 0.2 mM L-alanine, 20 M 3 H-OMG or 3 H-alanine, 0.10 mM MgSO4, 75 mM KC1, 50 mM mannitol, 100 mM of either NaCl or choline chloride, 10 M valinomycin, and 100 M carbonyl cyanide p-(tri-flouromethoxy)phenyl-hydrazone (FCCP).…”

Section: Drug Treatmentmentioning

confidence: 99%

“…A variety of hormones has also been demonstrated to alter NAcT in the mammalian small intestine (8). Although NAcT is inhibited in the chronically inflamed small intestine, it is of note that the mechanism of inhibition of this cotransport process is uniquely different from that of SGLT-1 during chronic ileitis (23). For example, during chronic ileitis, it has been demonstrated that whereas SGLT-1 inhibition is during chronic ileitis secondary to a decrease in cotransporter numbers, NAcT inhibition is secondary to a decrease in the affinity of the cotransporter for the amino acid without change in cotransporter numbers (23,24).…”

mentioning

confidence: 96%

“…For example, alanine is transported into villus cells by one of these Na-driven amino acid transporters specifically by the Na-neutral amino acid cotransporter system B 0 (Asct1)(3) and will be used to measure the effects of cNO on NAcT. Both cotransporters have been localized to the BBM of the absorptive villus but not the secretory crypt cells in the mammalian small intestine including rabbits (23,24). The favorable transcellular Na gradient for these secondary active transport processes is provided by Na-K-ATPase on the basolateral membrane (BLM) of villus cells (16).…”

mentioning

confidence: 99%

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Na-glucose and Na-neutral amino acid cotransport are uniquely regulated by constitutive nitric oxide in rabbit small intestinal villus cells

Coon¹,

Kim²,

Shao³

et al. 2005

American Journal of Physiology-Gastrointestinal and Liver Physi

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. Na-glucose and Na-neutral amino acid cotransport are uniquely regulated by constitutive nitric oxide in rabbit small intestinal villus cells. Am J Physiol Gastrointest Liver Physiol 289: G1030 -G1035, 2005. First published August 11, 2005; doi:10.1152/ajpgi.00124.2005.-Na-nutrient cotransport processes are not only important for the assimilation of essential nutrients but also for the absorption of Na in the mammalian small intestine. The effect of constitutive nitric oxide (cNO) on Na-glucose (SGLT-1) and Na-amino acid cotransport (NAcT) in the mammalian small intestine is unknown. Inhibition of cNO synthase with N G -nitro-L-arginine methyl ester (L-NAME) resulted in the inhibition of Na-stimulated 3 H-O-methyl-D-glucose uptake in villus cells. However, Na-stimulated alanine uptake was not affected in these cells. The L-NAME-induced reduction in SGLT-1 in villus cells was not secondary to an alteration in basolateral membrane Na-K-ATPase activity, which provides the favorable Na gradient for this cotransport process. In fact, SGLT-1 was inhibited in villus cell brush-border membrane (BBM) vesicles prepared from animals treated with L-NAME. Kinetic studies demonstrated that the mechanism of inhibition of SGLT-1 was secondary to a decrease in the affinity for glucose without a change in the maximal rate of uptake of glucose. Northern blot studies demonstrated no change in the mRNA levels of SGLT-1. Western blot studies demonstrated no significant change in the immunoreactive protein levels of SGLT-1 in ileal villus cell BBM from L-NAME-treated rabbits. These studies indicate that inhibition of cNO production inhibits SGLT-1 but not NAcT in the rabbit small intestine. Therefore, whereas cNO promotes Na-glucose cotransport, it does not affect NAcT in the mammalian small intestine. mucosal blood flow; glucose absorption; sodium absorption; intestinal absorption; regulation of intestinal glucose; amino acid absorption NITRIC OXIDE (NO) has been demonstrated to alter gastrointestinal functions in normal and pathophysiological states. In the normal gastrointestinal tract, NO has been demonstrated to alter motility, mucosal blood flow, mucus secretion, and intestinal electrolyte and fluid transport (18,26). We have previously demonstrated that inhibition of constitutive nitric oxide (cNO) synthase with N G -nitro-L-arginine methyl ester (L-NAME) resulted in the unique regulation of the three functionally different rabbit enterocyte brush border membrane (BBM) anion/HCO 3 exchangers. It did not affect villus cell BBM Cl/HCO 3 exchange; stimulated crypt cell BBM Cl/HCO 3 exchange; and inhibited villus cell BBM short-chain fatty acid (SCFA)/HCO 3 exchange. Furthermore, kinetic studies demonstrated that the mechanism of inhibition of crypt cell BBM Cl/HCO 3 exchange is secondary to a decrease in the maximal rate of uptake of Cl, without an alteration in the affinity of the transporter for Cl. However, in contrast, the mechanism of stimulation of villus cell BBM SCFA/HCO 3 exchange is secondary to an increase in the affin...

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Section: Drug Treatmentmentioning

confidence: 99%

Section: Drug Treatmentmentioning

confidence: 99%

Section: Drug Treatmentmentioning

confidence: 99%

mentioning

confidence: 96%

mentioning

confidence: 99%

See 3 more Smart Citations

Na-glucose and Na-neutral amino acid cotransport are uniquely regulated by constitutive nitric oxide in rabbit small intestinal villus cells

Coon¹,

Kim²,

Shao³

et al. 2005

American Journal of Physiology-Gastrointestinal and Liver Physi

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Transport of Solutes Across Biological Membranes in Eukaryotes: An Environmental Perspective

Handy

Eddy

2004

Physicochemical Kinetics and Transport at Biointerfaces

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Inhibitory effect of TNF‐α on the intestinal absorption of galactose

Amador¹,

García-Herrera²,

Marca³

et al. 2006

J of Cellular Biochemistry

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Sepsis is a systemic response to infection in which toxins, such as bacterial lipopolysaccharide (LPS), stimulate the production of inflammatory mediators like the cytokine tumor necrosis factor alpha (TNF-alpha). Previous studies from our laboratory have revealed that LPS inhibits the intestinal absorption of L-leucine and D-fructose in rabbit when it was intravenously administered, and that TNF-alpha seems to mediate this effect on amino acid absorption. To extend this work, the present study was designed to evaluate the possible effect of TNF-alpha on D-galactose intestinal absorption, identify the intracellular mechanisms involved and establish whether this cytokine mediates possible LPS effects. Our findings indicate that TNF-alpha decreases D-galactose absorption both in rabbit intestinal tissue preparations and brush-border membrane vesicles. Western blot analysis revealed reduced amounts of the Na+/glucose cotransporter (SGLT1) protein in the plasma membrane attributable to the cytokine. On the contrary, TNF-alpha increased SGLT1 mRNA levels. Specific inhibitors of the secondary messengers PKC, PKA, the MAP kinases p38 MAP, JNK, MEK1/2 as well as the proteasome, diminished the TNF-alpha-evoked inhibitory effect. LPS inhibition of the uptake of the sugar was blocked by a TNF-alpha antagonist. In conclusion, TNF-alpha inhibits D-galactose intestinal absorption by decreasing the number of SGLT1 molecules at the enterocyte plasma membrane through a mechanism in which several protein-like kinases are involved.

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Unique mechanism of inhibition of Na⁺-amino acid cotransport during chronic ileal inflammation

Cited by 38 publications

References 15 publications

Na-glucose and Na-neutral amino acid cotransport are uniquely regulated by constitutive nitric oxide in rabbit small intestinal villus cells

Na-glucose and Na-neutral amino acid cotransport are uniquely regulated by constitutive nitric oxide in rabbit small intestinal villus cells

Transport of Solutes Across Biological Membranes in Eukaryotes: An Environmental Perspective

Inhibitory effect of TNF‐α on the intestinal absorption of galactose

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Unique mechanism of inhibition of Na+-amino acid cotransport during chronic ileal inflammation

Cited by 38 publications

References 15 publications

Na-glucose and Na-neutral amino acid cotransport are uniquely regulated by constitutive nitric oxide in rabbit small intestinal villus cells

Na-glucose and Na-neutral amino acid cotransport are uniquely regulated by constitutive nitric oxide in rabbit small intestinal villus cells

Transport of Solutes Across Biological Membranes in Eukaryotes: An Environmental Perspective

Inhibitory effect of TNF‐α on the intestinal absorption of galactose

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Product

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Unique mechanism of inhibition of Na⁺-amino acid cotransport during chronic ileal inflammation