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T1737 Inducible Nitric Oxide Uniquely Regulates Na-Glutamine Co-Transporters B0AT1 in Villus Cells and SN2 in Crypt Cells During Chronic Enteritis
Villus and crypt cells were isolated from the rabbit intestine by a Ca++ chelation technique. l-N(6)-(1-Iminoethyl)-lysine (L-NIL) was administered intramuscularly to selectively inhibit iNOS In Vivo. Brush border membrane vesicles (BBMV) were prepared from cells by Ca++ precipitation and differential centrifugation. Uptake studies were done by rapid filtration technique using 3H-glutamine. Western blot studies were performed of BBM using specific antibodies. RESULTS: In intact villus cells NGcT which was inhibited in the chronically inflamed intestine was reversed by treatment with L-NIL (121±15 pmol/mg protein/2 mins in normal; 50.6±4.8 in inflamed; 163±27.3 in inflamed+NIL, p<0.05, n=4). In contrast, in crypt cells NGcT which was stimulated during chronic enteritis was restored to its normal levels by treatment with L-NIL (67±4.9 pmol/mg protein/2 min in normal; 134.3±12.5 in inflamed; 72.8±5.2 in inflamed+L-NIL, p<0.05, n=4). Na/K ATPase which provides the favorable Na gradient for the transporters was also restored to its normal levels by L-NIL in both villus and crypt cells (data not shown). BBMV uptake studies also showed that LNIL reversed the inhibition of B0AT1 in villus cells (112.7±0.5 pmol/mg protein/30secs in normal; 23.4±1.8 in inflamed; 132±24 in inflamed+L-NIL) and the stimulation of SN2 in crypt cells during chronic enteritis (34±6.2 pmol/mg protein/90secs in normal; 132±10 in inflamed; 55±3.5 in inflamed+L-NIL, p<0.05, n=3). Kinetic studies demonstrated that LNIL reversed the inhibition of NGcT in villus cells by restoring the diminished co-transporter numbers and in the crypt cells by restoring the enhanced affinity of the co-transporter for glutamine. Western blot studies showed that L-NIL restored B0AT1 to normal levels in villus cell BBM while SN2 levels remained unchanged in crypt cell BBM during chronic enteritis. CONCLUSION: Inhibition of iNO in the chronically inflamed intestine reversed the unique alterations in B0AT1 in villus and SN2 in crypts. These data indicate that iNO likely mediates its activity as a common upstream immune regulator of these two different Na-glutamine co-transporters.
Ursodeoxycholic Acid Exerts Antisecretory Actions On Colonic Epithelial Cells Orlaith B. Kelly, Niamh Keating, Michael Scharl, Kate Keaveney, Frank E. Murray, Alan F. Hofmann, Stephen J. Keely Background: The primary bile acid, chenodeoxycholic acid (CDCA), is known to stimulate colonic fluid and electrolyte secretion. Increased colonic delivery of CDCA is likely to contribute to diarrhea associated with conditions of bile acid malabsorption. However, CDCA is metabolised by colonic bacteria to ursodeoxycholic acid (UDCA) and lithocholic acid (LCA) and little is known of the effects of these secondary bile acids on colonic secretory function. Aims: To investigate the effects of UDCA on colonic epithelial secretory function. Methods: Cl- secretion was measured as changes in short circuit current (Isc) across voltageclamped monolayers of T84 cells in Ussing chambers. Results: At high concentrations (500 μM- mM) CDCA rapidly stimulated Cl- secretion. In contrast, UDCA (50 μM-1 mM) was devoid of prosecretory activity. However, pretreatment of T84 cells with UDCA (500μM) significantly attenuated subsequent secretory responses to the Ca2+-dependent agonist, carbachol (CCh; 100 μM) and the cAMP-dependent agonist, forskolin (10 μM) to 11.9 ± 4.2% (n=9; p<0.001) and 43.0 ± 13.0% ( n=6; p< 0.05), respectively. The effects of UDCA were concentration-dependent with antisecretory actions apparent at concentrations as low as 50 μM. However, even at concentrations of 1 mM, UDCA did not alter transepithelial resistance implying it did not exert toxic effects. UDCA was more effective in inhibiting CCh-stimulated secretory responses when added to the basolateral side of cells. In further experiments we measured Na/K-ATPase pump activity in apically permeabilised monolayers and found that UDCA inhibited Na/K-ATPase pump activity to 16.2 ± 3.9% of that in control cells (n=4; p<0.001). Similar to UDCA, LCA was also without effect on basal Clsecretion in T84 cells. However, pretreatment of cells with LCA (50-200 μM) significantly potentiated responses to CCh. LCA (100 μM) increased CCh-induced responses to 146.67 ± 8.7% of those in controls (n = 8; p < 0.001). However, at concentrations >500μM, LCA exerted antisecretory actions similar to UDCA. Conclusion: Our data indicate that bacterial metabolism of CDCA alters its ability to regulate colonic secretion. While UDCA exerts purely antisecretory effects, LCA enhances secretion at relatively low concentrations but is antisecretory at high concentrations. Thus, alterations in relative levels of CDCA, UDCA and LCA in the colon, whether under normal or pathological conditions, are likely to alter epithelial secretory function. Our data also suggest that manipulation of individual bile acid levels through the use of antibiotics or probiotics may prove to be useful approach for treating intestinal transport disorders.
T1738 The Mechanism of Inhibition of Na-K-ATPase On the Basolateral Membrane of Villus Cells in the Chronically Inflamed Small Intestine Prosenjit Saha, Ramesh Kekuda, Uma Sundaram BACKGROUND: Na-K-ATPase, on the basolateral membrane (BLM) of mammalian intestinal epithelial cells provides the favorable intracellular Na+ gradient to promote all Na+ dependent co-transport processes. This is a transmembrane heterodimer protein composed of α and β subunits. The functional capacity of Na-K-ATPase complex resides in the α-1 subunit while β-1 subunit is involved in stabilizing the correct folding of the α-1 polypeptide. Ankyrin-spectrin skeleton is involved in the trafficking and retention of Na-K-ATPase at the BLM. Inhibition of Na-K-ATPase activity and resultant inhibition of a variety of Na-solute co-transporters have been reported in the chronically inflamed mammalian intestine. But the mechanism of inhibition of Na-K-ATPase is not known. AIM: Determine the mechanism of inhibition of Na-K-ATPase during chronic enteritis. METHOD: Rabbit model of chronic enteritis induced by Eimeria magna was used for these studies. Villus cells were isolated from the intestine by a Ca++ chelation technique. α-1, β-1, ankyrin and spectrin mRNA abundance, protein expression and interaction were analyzed by RTQ-PCR, Western blot, immunocytochemistry and immunoprecipitation techniques. RESULTS: RTQ-PCR results demonstrated that mRNA levels of α-1 and β-1 were not altered in villus cells during chronic intestinal inflammation. Western blot showed that immune reactive protein levels of α-1 and β-1 were also not altered in the cytosol. However, both were significantly (n=3 p<0.01) reduced (50%) in BLM from villus cells from chronically inflamed intestine. The results of immunocytochemistry using confocal microscope also showed diminished localization of α-1 and β-1 in BLM during chronic inflammation. Ankyrin mRNA abundance and protein expression were inhibited (60%) during inflammation (n=6, p<0.01) whereas spectrin expression was not altered. Immunoprecipitated α-1 protein showed reduced levels of ankyrin expression during chronic enteritis, which indicates the loss of interaction between α-1 and ankyrin. Dual immunocytochemistry with α-1 and ankyrin also showed decreased localization of α-1 in BLM associated with ankyrin expression. CONCLUSION: In villus cells from the chronically inflamed intestine inhibition of Na-K-ATPase activity in the BLM is secondary to reduced ankyrin, but not spectrin, or α-1 or β-1 subunits of Na-K-ATPase. Diminished ankyrin in turn inhibits spectrin-ankyrin complex association with α-1 subunit of Na-KATPase and trafficking to the BLM, thus resulting in the inhibition of Na-K-ATPase during chronic enteritis.
T1736 Mechanism of Inhibition of Na-Alanine Co-Transport By Leukotriene D4 in Intestinal Epithelial Cells Jamilur R. Talukder, Ramesh Kekuda, Uma Sundaram Background: Lipoxygenase pathway metabolite leukotriene D4 (LTD4) inhibits Na-dependent alanine co-transport (ASCT1) in intestinal epithelial cell brush border membrane (BBM) by decreasing the affinity of co-transporter. However, the intracellular mechanism of LTD4 mediated inhibition of ASCT1 is unknown. Aim: Determine the intracellular mechanism of regulation of ASCT1 inhibition by LTD4 in enterocytes. Methods: Rat small intestinal epithelial cells (IEC-18) monolayers grown on transwell plates were utilized. Cells were treated with placebo or LTD4, and/or inhibitors of PKG, PKA, PKC and Akt pathways for 48 hours. Na-dependent [3H]-alaninie uptake was measured to determine ASCT1 activity. cAMP levels were determined by EIA and cytosolic Ca2+ concentration using Fluo-3AM. ASCT1 mRNA was quantitated by RTQ-PCR. Results: LTD4 decreased ASCT1 activity in IEC-18 (7.1±0.1 nmol/mg prot/2 min in control and 2.9±0.1 in LTD4 treated cells, n=4, p<0.01). LTD4 treatment increased intracellular cAMP (416±22 pmol/mg protein in control and 1176±44 in treated cells, n=6, p<0.01). However, protein kinase A inhibitor Rp-MB-cAMP did not reverse the LTD4 mediated inhibition of ASCT1. But LTD4 increased cytosolic Ca2+ (2fold) in IEC-18 cells. Also PKC inhibitor (Calphostin C) fully reversed LTD4 mediated inhibition of ASCT1 in IEC-18 cells (6.93±0.1 nmol/mg protein/2 min, n=4, p<0.01). Further, inhibition of PKC-α with Gö 6976 reversed LTD4 mediated inhibition of ASCT1 in IEC18 cells (6.9±0.1 nmol/mg protein/2 min in LTD4 + Gö 6976 treated cells, n=4, p<0.01). In contrast, PKC-ε and PKC-δ inhibitors (Rottlerin) did not reverse LTD4 mediated inhibition of ASCT1 in IEC-18 cells (data not shown). Further, downstream of PKC-α pathway, Akt inhibitor (1L6-Hydroxymethyl-chiro-inositol-2-(R)-2-O-methyl-3-O-octadecyl-sn-glycerocarbonate) also reversed LTD4 mediated inhibition of ASCT1 in IEC-18 cells (6.9±0.1 nmol/ mg prot/2 min in LTD4 + Akt inhibitor treated cells, n=4, p< 0.05). LTD4 inhibits ASCT1 secondary to a decrease in affinity of co-transporter. Kinetic studies demonstrated that the mechanism of reversal of LTD4 mediated inhibition of ASCT1 by Akt inhibitor in IEC-18 cells was secondary to the restoration of affinity of the co-transporter without a change in Vmax. Consistent with this RTQ-PCR studies demonstrated that mRNA levels remained unaltered in both LTD4, and Akt inhibitor-LTD4 treated cells. Conclusions: These studies demonstrated that while LTD4 increased intracellular cAMP and Ca++ levels, inhibition of ASCT1 appears to be mediated by Ca-dependent PKC in IEC-18 cells. Specifically, LTD4 inhibits ASCT1 via PKC-α then Akt in intestinal epithelial cells.
T1739 Selective Regulation of Na+-K+-2cl- Cotransporter Surface Expression and Epithelial Cl- Secretion By Novel Protein Kinase C (PKC) Isoforms δ and ε Jun Tang, Patrice Bouyer, Andreas Mykoniatis, Mary M. Buschmann, Xu Tang, Karl S. Matlin, Jeffrey B. Matthews The Na+-K+-2Cl- cotransporter (NKCC1) drives basolateral Cl- entry in secretory epithelia and is a key determinant of diarrheal responses in various enteropathies. In native colon and model human T84 colonic epithelia, activation of PKC by phorbol 12-myristate 13acetate (PMA) or the muscarinic agent carbachol reduces the Cl- secretory response to cAMP in parallel with both functional inhibition and loss of surface expression of NKCC1. Aim: To use RNA interference to define isoform selectivity of PKC inhibition of NKCC1 and Clsecretion. Methods: Adenoviral vectors expressing human PKC isoform-specific shRNAs (α, δ, ε) or non-targeting LacZ-shRNA were generated. To assess the impact of PKC isoform knockdown, uninfected and shRNA virus-infected T84 monolayers were incubated with 100nM PMA or DMSO for 1h, followed by cAMP stimulation with 10μM forskolin. Clsecretion was measured by voltage/current clamp as the short-circuit current (Isc). NKCC1 surface expression was determined by indirect immunofluorescence using T4 antibody; monolayers were fixed, permeabilized, stained and visualized by confocal microscopy. NKCC1 surface expression was further studied by selective basolateral membrane biotinylation and Western blot. Results: Specific knockdown by adenoviral shRNA selectively reduced PKCα, PKCδ and PKCε protein levels by ~ 90% after 72h of viral transduction. PMA reduced cAMP-dependent Cl- secretion (Isc) by 48.4% in uninfected controls (n=17), 42.1% in LacZ-shRNA (n=17, p>0.05 vs. the uninfected), and 41% in PKCα-shRNA (n= 14, p>0.05). However, knockdown of PKCδ and PKCε prevented this action of PMA: Isc
T1737 Inducible Nitric Oxide Uniquely Regulates Na-Glutamine Co-Transporters B0AT1 in Villus Cells and SN2 in Crypt Cells During Chronic Enteritis Subha Arthur, Uma Sundaram BACKGROUND: B0AT1 which mediates Na-glutamine co-transport (NGcT) in villus cells is inhibited while SN2 which does the same in crypt cells is stimulated in a rabbit model of chronic intestinal inflammation. How inducible nitric oxide (iNO), known to be increased in the mucosa of rabbits with chronic enteritis, may regulate these two co-transporters during chronic enteritis is not known AIM: Determine the effect of inhibition of iNO synthase (iNOS) on B0AT1 in villus cells and SN2 in crypt cells during chronic enteritis METHODS:
A-569
AGA Abstracts
AGA Abstracts
T1735
Ursodeoxycholic Acid Exerts Antisecretory Actions On Colonic Epithelial Cells Orlaith B. Kelly, Niamh Keating, Michael Scharl, Kate Keaveney, Frank E. Murray, Alan F. Hofmann, Stephen J. Keely Background: The primary bile acid, chenodeoxycholic acid (CDCA), is known to stimulate colonic fluid and electrolyte secretion. Increased colonic delivery of CDCA is likely to contribute to diarrhea associated with conditions of bile acid malabsorption. However, CDCA is metabolised by colonic bacteria to ursodeoxycholic acid (UDCA) and lithocholic acid (LCA) and little is known of the effects of these secondary bile acids on colonic secretory function. Aims: To investigate the effects of UDCA on colonic epithelial secretory function. Methods: Cl- secretion was measured as changes in short circuit current (Isc) across voltageclamped monolayers of T84 cells in Ussing chambers. Results: At high concentrations (500 μM- mM) CDCA rapidly stimulated Cl- secretion. In contrast, UDCA (50 μM-1 mM) was devoid of prosecretory activity. However, pretreatment of T84 cells with UDCA (500μM) significantly attenuated subsequent secretory responses to the Ca2+-dependent agonist, carbachol (CCh; 100 μM) and the cAMP-dependent agonist, forskolin (10 μM) to 11.9 ± 4.2% (n=9; p<0.001) and 43.0 ± 13.0% ( n=6; p< 0.05), respectively. The effects of UDCA were concentration-dependent with antisecretory actions apparent at concentrations as low as 50 μM. However, even at concentrations of 1 mM, UDCA did not alter transepithelial resistance implying it did not exert toxic effects. UDCA was more effective in inhibiting CCh-stimulated secretory responses when added to the basolateral side of cells. In further experiments we measured Na/K-ATPase pump activity in apically permeabilised monolayers and found that UDCA inhibited Na/K-ATPase pump activity to 16.2 ± 3.9% of that in control cells (n=4; p<0.001). Similar to UDCA, LCA was also without effect on basal Clsecretion in T84 cells. However, pretreatment of cells with LCA (50-200 μM) significantly potentiated responses to CCh. LCA (100 μM) increased CCh-induced responses to 146.67 ± 8.7% of those in controls (n = 8; p < 0.001). However, at concentrations >500μM, LCA exerted antisecretory actions similar to UDCA. Conclusion: Our data indicate that bacterial metabolism of CDCA alters its ability to regulate colonic secretion. While UDCA exerts purely antisecretory effects, LCA enhances secretion at relatively low concentrations but is antisecretory at high concentrations. Thus, alterations in relative levels of CDCA, UDCA and LCA in the colon, whether under normal or pathological conditions, are likely to alter epithelial secretory function. Our data also suggest that manipulation of individual bile acid levels through the use of antibiotics or probiotics may prove to be useful approach for treating intestinal transport disorders.
T1738 The Mechanism of Inhibition of Na-K-ATPase On the Basolateral Membrane of Villus Cells in the Chronically Inflamed Small Intestine Prosenjit Saha, Ramesh Kekuda, Uma Sundaram BACKGROUND: Na-K-ATPase, on the basolateral membrane (BLM) of mammalian intestinal epithelial cells provides the favorable intracellular Na+ gradient to promote all Na+ dependent co-transport processes. This is a transmembrane heterodimer protein composed of α and β subunits. The functional capacity of Na-K-ATPase complex resides in the α-1 subunit while β-1 subunit is involved in stabilizing the correct folding of the α-1 polypeptide. Ankyrin-spectrin skeleton is involved in the trafficking and retention of Na-K-ATPase at the BLM. Inhibition of Na-K-ATPase activity and resultant inhibition of a variety of Na-solute co-transporters have been reported in the chronically inflamed mammalian intestine. But the mechanism of inhibition of Na-K-ATPase is not known. AIM: Determine the mechanism of inhibition of Na-K-ATPase during chronic enteritis. METHOD: Rabbit model of chronic enteritis induced by Eimeria magna was used for these studies. Villus cells were isolated from the intestine by a Ca++ chelation technique. α-1, β-1, ankyrin and spectrin mRNA abundance, protein expression and interaction were analyzed by RTQ-PCR, Western blot, immunocytochemistry and immunoprecipitation techniques. RESULTS: RTQ-PCR results demonstrated that mRNA levels of α-1 and β-1 were not altered in villus cells during chronic intestinal inflammation. Western blot showed that immune reactive protein levels of α-1 and β-1 were also not altered in the cytosol. However, both were significantly (n=3 p<0.01) reduced (50%) in BLM from villus cells from chronically inflamed intestine. The results of immunocytochemistry using confocal microscope also showed diminished localization of α-1 and β-1 in BLM during chronic inflammation. Ankyrin mRNA abundance and protein expression were inhibited (60%) during inflammation (n=6, p<0.01) whereas spectrin expression was not altered. Immunoprecipitated α-1 protein showed reduced levels of ankyrin expression during chronic enteritis, which indicates the loss of interaction between α-1 and ankyrin. Dual immunocytochemistry with α-1 and ankyrin also showed decreased localization of α-1 in BLM associated with ankyrin expression. CONCLUSION: In villus cells from the chronically inflamed intestine inhibition of Na-K-ATPase activity in the BLM is secondary to reduced ankyrin, but not spectrin, or α-1 or β-1 subunits of Na-K-ATPase. Diminished ankyrin in turn inhibits spectrin-ankyrin complex association with α-1 subunit of Na-KATPase and trafficking to the BLM, thus resulting in the inhibition of Na-K-ATPase during chronic enteritis.
T1736 Mechanism of Inhibition of Na-Alanine Co-Transport By Leukotriene D4 in Intestinal Epithelial Cells Jamilur R. Talukder, Ramesh Kekuda, Uma Sundaram Background: Lipoxygenase pathway metabolite leukotriene D4 (LTD4) inhibits Na-dependent alanine co-transport (ASCT1) in intestinal epithelial cell brush border membrane (BBM) by decreasing the affinity of co-transporter. However, the intracellular mechanism of LTD4 mediated inhibition of ASCT1 is unknown. Aim: Determine the intracellular mechanism of regulation of ASCT1 inhibition by LTD4 in enterocytes. Methods: Rat small intestinal epithelial cells (IEC-18) monolayers grown on transwell plates were utilized. Cells were treated with placebo or LTD4, and/or inhibitors of PKG, PKA, PKC and Akt pathways for 48 hours. Na-dependent [3H]-alaninie uptake was measured to determine ASCT1 activity. cAMP levels were determined by EIA and cytosolic Ca2+ concentration using Fluo-3AM. ASCT1 mRNA was quantitated by RTQ-PCR. Results: LTD4 decreased ASCT1 activity in IEC-18 (7.1±0.1 nmol/mg prot/2 min in control and 2.9±0.1 in LTD4 treated cells, n=4, p<0.01). LTD4 treatment increased intracellular cAMP (416±22 pmol/mg protein in control and 1176±44 in treated cells, n=6, p<0.01). However, protein kinase A inhibitor Rp-MB-cAMP did not reverse the LTD4 mediated inhibition of ASCT1. But LTD4 increased cytosolic Ca2+ (2fold) in IEC-18 cells. Also PKC inhibitor (Calphostin C) fully reversed LTD4 mediated inhibition of ASCT1 in IEC-18 cells (6.93±0.1 nmol/mg protein/2 min, n=4, p<0.01). Further, inhibition of PKC-α with Gö 6976 reversed LTD4 mediated inhibition of ASCT1 in IEC18 cells (6.9±0.1 nmol/mg protein/2 min in LTD4 + Gö 6976 treated cells, n=4, p<0.01). In contrast, PKC-ε and PKC-δ inhibitors (Rottlerin) did not reverse LTD4 mediated inhibition of ASCT1 in IEC-18 cells (data not shown). Further, downstream of PKC-α pathway, Akt inhibitor (1L6-Hydroxymethyl-chiro-inositol-2-(R)-2-O-methyl-3-O-octadecyl-sn-glycerocarbonate) also reversed LTD4 mediated inhibition of ASCT1 in IEC-18 cells (6.9±0.1 nmol/ mg prot/2 min in LTD4 + Akt inhibitor treated cells, n=4, p< 0.05). LTD4 inhibits ASCT1 secondary to a decrease in affinity of co-transporter. Kinetic studies demonstrated that the mechanism of reversal of LTD4 mediated inhibition of ASCT1 by Akt inhibitor in IEC-18 cells was secondary to the restoration of affinity of the co-transporter without a change in Vmax. Consistent with this RTQ-PCR studies demonstrated that mRNA levels remained unaltered in both LTD4, and Akt inhibitor-LTD4 treated cells. Conclusions: These studies demonstrated that while LTD4 increased intracellular cAMP and Ca++ levels, inhibition of ASCT1 appears to be mediated by Ca-dependent PKC in IEC-18 cells. Specifically, LTD4 inhibits ASCT1 via PKC-α then Akt in intestinal epithelial cells.
T1739 Selective Regulation of Na+-K+-2cl- Cotransporter Surface Expression and Epithelial Cl- Secretion By Novel Protein Kinase C (PKC) Isoforms δ and ε Jun Tang, Patrice Bouyer, Andreas Mykoniatis, Mary M. Buschmann, Xu Tang, Karl S. Matlin, Jeffrey B. Matthews The Na+-K+-2Cl- cotransporter (NKCC1) drives basolateral Cl- entry in secretory epithelia and is a key determinant of diarrheal responses in various enteropathies. In native colon and model human T84 colonic epithelia, activation of PKC by phorbol 12-myristate 13acetate (PMA) or the muscarinic agent carbachol reduces the Cl- secretory response to cAMP in parallel with both functional inhibition and loss of surface expression of NKCC1. Aim: To use RNA interference to define isoform selectivity of PKC inhibition of NKCC1 and Clsecretion. Methods: Adenoviral vectors expressing human PKC isoform-specific shRNAs (α, δ, ε) or non-targeting LacZ-shRNA were generated. To assess the impact of PKC isoform knockdown, uninfected and shRNA virus-infected T84 monolayers were incubated with 100nM PMA or DMSO for 1h, followed by cAMP stimulation with 10μM forskolin. Clsecretion was measured by voltage/current clamp as the short-circuit current (Isc). NKCC1 surface expression was determined by indirect immunofluorescence using T4 antibody; monolayers were fixed, permeabilized, stained and visualized by confocal microscopy. NKCC1 surface expression was further studied by selective basolateral membrane biotinylation and Western blot. Results: Specific knockdown by adenoviral shRNA selectively reduced PKCα, PKCδ and PKCε protein levels by ~ 90% after 72h of viral transduction. PMA reduced cAMP-dependent Cl- secretion (Isc) by 48.4% in uninfected controls (n=17), 42.1% in LacZ-shRNA (n=17, p>0.05 vs. the uninfected), and 41% in PKCα-shRNA (n= 14, p>0.05). However, knockdown of PKCδ and PKCε prevented this action of PMA: Isc
T1737 Inducible Nitric Oxide Uniquely Regulates Na-Glutamine Co-Transporters B0AT1 in Villus Cells and SN2 in Crypt Cells During Chronic Enteritis Subha Arthur, Uma Sundaram BACKGROUND: B0AT1 which mediates Na-glutamine co-transport (NGcT) in villus cells is inhibited while SN2 which does the same in crypt cells is stimulated in a rabbit model of chronic intestinal inflammation. How inducible nitric oxide (iNO), known to be increased in the mucosa of rabbits with chronic enteritis, may regulate these two co-transporters during chronic enteritis is not known AIM: Determine the effect of inhibition of iNO synthase (iNOS) on B0AT1 in villus cells and SN2 in crypt cells during chronic enteritis METHODS:
A-569
AGA Abstracts
AGA Abstracts
T1735