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Na+ Absorption (na+ + absorption)
Selected AbstractsGallbladder Na+/H+ exchange activity is up-regulated prior to cholesterol crystal formationEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 8 2005S. C. Narins Abstract Background, Gallbladder Na+ and H2O absorption are increased prior to gallstone formation and may promote cholesterol nucleation. Na+/H+ exchange (NHE) isoforms NHE2 and NHE3 are involved in gallbladder Na+ transport in prairie dogs. We examined whether increased gallbladder Na+ absorption observed during early gallstone formation is the result of NHE up-regulation. Materials and methods, Native gallbladder and primary cultures of gallbladder epithelial cells (GBECs) harvested from prairie dogs fed nonlithogenic (CON) or 1·2% cholesterol diet for varying lengths of time to induce cholesterol-saturated bile (PreCRYS), cholesterol crystals (CRYS), or gallstones (GS) were used. NHE activity was assessed by measuring dimethylamiloride-inhibitable 22Na+ uptake under H+ gradient in primary GBECs. HOE-694 was used to determine NHE2 and NHE3 contributions. NHE protein and mRNA expression were examined by Western and Northern blots, respectively. Results, Gallbladder total NHE activity was 25·1 ± 1·3 nmol mg protein,1 min,1 in the control and increased during gallstone formation peaking at the PreCRYS stage (98·4 ± 3·9 nmol mg protein,1 min,1). There was a shift in NHE activity from NHE2 to NHE3 as the animals progressed from no stones through the PreCRYS and CRYS stages to gallstones. The increase in NHE activity was partly caused by an increased Vmax without any change in KNam. Both NHE2 and NHE3 protein increased moderately during the PreCRYS stage without increases in mRNA expression. Conclusions, Increased gallbladder Na+ absorption observed prior to crystal formation is in part caused by an increase NHE activity which is not fully accounted for by an increase in NHE proteins and mRNA levels but may be explained by enhanced localization in the membranes and/or altered regulation of NHE. [source] Preserved Na+/H+ exchanger isoform 3 expression and localization, but decreased NHE3 function indicate regulatory sodium transport defect in ulcerative colitis,INFLAMMATORY BOWEL DISEASES, Issue 7 2010Sunil Yeruva PhD Abstract Background: A major causative factor of diarrhea in ulcerative colitis (UC) patients is the loss of Na+ absorptive capacity of the inflamed colonic mucosa. Potential contributing mechanisms include reduced driving force for active transport, and impaired expression, mislocalization, or defective transport function of Na+ absorptive proteins. We therefore studied the expression, brush border membrane (BBM) localization, and transport capacity of the major intestinal Na+ absorptive protein, the Na+/H+ exchanger isoform 3 (NHE3) in biopsies from UC patients. Methods: In UC and control biopsies, inflammation was graded histologically, NHE3, tumor necrosis factor alpha (TNF-,), villin, as well as other housekeeping genes were analyzed by quantitative real-time polymerase chain reaction (PCR), BBM localization of NHE3 determined by immunohistochemistry, and confocal microscopy. Na+ absorptive capacity was assessed by 22Na+ isotope fluxes and NHE3 transport activity measured microfluorometrically in BCECF-loaded surface colonocytes within isolated crypts. Results: In mildly, moderately, and severely inflamed sigmoid colon of UC patients, neither NHE3 mRNA expression nor the abundance of NHE3 in the BBM was significantly altered compared to other structural components of the BBM. However, Na+ absorption was strongly reduced by ,80% and acid-activated NHE3 transport activity was significantly decreased in the surface cells of sigmoid colonic crypts even in moderately inflamed mucosa. Conclusions: In the colonic mucosa of patients with active UC, NHE3 transport capacity was found significantly decreased despite correct NHE3 location and abundance in the brush border, independent of current treatment. These findings suggest functional NHE3 transport as a novel factor for inflammatory diarrhea in UC patients. (Inflamm Bowel Dis 2010) [source] Cultivation of medicinal isabgol (Plantago ovata) in alkali soils in semiarid regions of Northern IndiaLAND DEGRADATION AND DEVELOPMENT, Issue 3 2006J. C. Dagar Abstract There is growing global demand for medicinal drugs including isabgol (Plantago ovata). With increasing demand of food for an ever-increasing population in India, it is not possible to bring arable lands under cultivation for aromatic and medicinal plants. Salt-affected lands (both saline and alkali) occupy about 8·6 million ha. Due to poor physical properties and excessive exchangeable Na+, most of these lands do not support good vegetation cover. The marginal and salt-affected lands could be successfully utilized for the cultivation of aromatic and medicinal plants. We achieved almost complete germination of isabgol seeds using up to 5000,ppm salt-solution. Grain yield (including husk) was 1·47 to 1·58,t,ha,1 at pH 9·2 showing no significant yield reduction as compared to normal soil. At pH 9·6 the grain yield was 1·03 to 1·12,t,ha,1. At higher pH there was significant reduction in yield. Sowing in good moisture (at field capacity) of soil was found best, but to save time sowing at shallow depth in dry soil, followed by irrigation was also suitable as compared to broadcasting seeds. The chlorophyll content was greater 70 days after sowing compared to younger stages (50 days after sowing). The total chlorophyll and plant biomass were lower from crops grown by broadcasting methods of sowing as compared to two other methods of sowing. The leaf area index (LAI) was higher for the broadcasting method of sowing as compared to the other two methods. Na+ absorption increased and K+ and K+/Na+ ratio decreased with increase in pH. Results reported in this paper clearly indicate that isabgol can successfully be grown on moderately alkali soils up to pH 9·6 without the application of any amendment. Copyright © 2006 John Wiley & Sons, Ltd. [source] Aldosterone responsiveness of the epithelial sodium channel (ENaC) in colon is increased in a mouse model for Liddle's syndromeTHE JOURNAL OF PHYSIOLOGY, Issue 2 2008Marko Bertog Liddle's syndrome is an autosomal dominant form of human hypertension, caused by gain-of-function mutations of the epithelial sodium channel (ENaC) which is expressed in aldosterone target tissues including the distal colon. We used a mouse model for Liddle's syndrome to investigate ENaC-mediated Na+ transport in late distal colon by measuring the amiloride-sensitive transepithelial short circuit current (,ISC-Ami) ex vivo. In Liddle mice maintained on a standard salt diet, ,ISC-Ami was only slightly increased but plasma aldosterone (PAldo) was severely suppressed. Liddle mice responded to a low or a high salt diet by increasing or decreasing, respectively, their PAldo and ,ISC-Ami. However, less aldosterone was required in Liddle animals to achieve similar or even higher Na+ transport rates than wild-type animals. Indeed, the ability of aldosterone to stimulate ,ISC-Ami was about threefold higher in Liddle animals than in the wild-type controls. Application of aldosterone to colon tissue in vitro confirmed that ENaC stimulation by aldosterone was not only preserved but enhanced in Liddle mice. Aldosterone-induced transcriptional up-regulation of the channel's ,- and ,-subunit (,ENaC and ,ENaC) and of the serum- and glucocorticoid-inducible kinase 1 (SGK1) was similar in colon tissue from Liddle and wild-type animals, while aldosterone had no transcriptional effect on the ,-subunit (,ENaC). Moreover, Na+ feedback regulation was largely preserved in colon tissue of Liddle animals. In conclusion, we have demonstrated that in the colon of Liddle mice, ENaC-mediated Na+ transport is enhanced with an increased responsiveness to aldosterone. This may be pathophysiologically relevant in patients with Liddle's syndrome, in particular on a high salt diet, when suppression of PAldo is likely to be insufficient to reduce Na+ absorption to an appropriate level. [source] Effects of nominally selective inhibitors of the kinases PI3K, SGK1 and PKB on the insulin-dependent control of epithelial Na+ absorptionBRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2010Morag K Mansley BACKGROUND AND PURPOSE Insulin-induced Na+ retention in the distal nephron may contribute to the development of oedema/hypertension in patients with type 2 diabetes. This response to insulin is usually attributed to phosphatidylinositol-3-kinase (PI3K)/serum and glucocorticoid-inducible kinase 1 (SGK1) but a role for protein kinase B (PKB) has been proposed. The present study therefore aimed to clarify the way in which insulin can evoke Na+ retention. EXPERIMENTAL APPROACH We examined the effects of nominally selective inhibitors of PI3K (wortmannin, PI103, GDC-0941), SGK1 (GSK650394A) and PKB (Akti-1/2) on Na+ transport in hormone-deprived and insulin-stimulated cortical collecting duct (mpkCCD) cells, while PI3K, SGK1 and PKB activities were assayed by monitoring the phosphorylation of endogenous proteins. KEY RESULTS Wortmannin substantially inhibited basal Na+ transport whereas PI103 and GDC-0941 had only very small effects. However, these PI3K inhibitors all abolished insulin-induced Na+ absorption and inactivated PI3K, SGK1 and PKB fully. GSK650394A and Akti-1/2 also inhibited insulin-evoked Na+ absorption and while GSK650394A inhibited SGK1 without affecting PKB, Akti-1/2 inactivated both kinases. CONCLUSION AND IMPLICATIONS While studies undertaken using PI103 and GDC-0941 show that hormone-deprived cells can absorb Na+ independently of PI3K, PI3K seems to be essential for insulin induced Na+ transport. Akti-1/2 does not act as a selective inhibitor of PKB and data obtained using this compound must therefore be treated with caution. GSK650394A, on the other hand, selectively inhibits SGK1 and the finding that GSK650394A suppressed insulin-induced Na+ absorption suggests that this response is dependent upon signalling via PI3K/SGK1. [source] REGULATION OF EPITHELIAL Na+ CHANNELS BY ALDOSTERONE: ROLE OF Sgk1CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 2 2008Il-Ha Lee SUMMARY 1The epithelial sodium channel (ENaC) is tightly regulated by hormonal and humoral factors, including cytosolic ion concentration and glucocorticoid and mineralocorticoid hormones. Many of these regulators of ENaC control its activity by regulating its surface expression via neural precursor cell-expressed developmentally downregulated (gene 4) protein (Nedd4-2). 2During the early phase of aldosterone action, Nedd4-2-dependent downregulation of ENaC is inhibited by the serum- and glucocorticoid-induced kinase 1 (Sgk1). 3Sgk1 phosphorylates Nedd4-2. Subsequently, phosphorylated Nedd4-2 binds to the 14-3-3 protein and, hence, reduces binding of Nedd4-2 to ENaC. 4Nedd4-2 is also phosphorylated by protein kinase B (Akt1). Both Sgk1 and Akt1 are part of the insulin signalling pathway that increases transepithelial Na+ absorption by inhibiting Nedd4-2 and activating ENaC. [source] Pharmacotherapy Of The Ion Transport Defect In Cystic FibrosisCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2001Karl Kunzelmann SUMMARY 1. More than 1300 different mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) cause cystic fibrosis (CF), a disease characterized by deficient epithelial Cl, secretion and enhanced Na+ absorption. The clinical course of the disease is determined by the progressive lung disease. Thus, novel approaches in pharmacotherapy are based primarily on correction of the ion transport defect in the airways. 2. The current therapeutic strategies try to counteract the deficiency in Cl, secretion and the enhanced Na+ absorption. A number of compounds have been identified, such as genistein and xanthine derivatives, which directly activate mutant CFTR. Other compounds may activate alternative Ca2+ -activated Cl, channels or basolateral K+ channels, which supply the driving force for Cl, secretion. Apart from that, Na+ channel blockers, such as phenamil and benzamil, are being explored, which counteract the hyperabsorption of NaCl in CF airways. 3. Clinical trials are under way using purinergic compounds such as the P2Y2 receptor agonist INS365. Activation of P2Y2 receptors has been found to both activate Cl, secretion and inhibit Na+ absorption. 4. The ultimate goal is to recover Cl, channel activity of mutant CFTR by either enhancing synthesis and expression of the protein or by activating silent CFTR Cl, channels. Strategies combining these drugs with compounds facilitating Cl, secretion and inhibiting Na+ absorption in vivo may have the best chance to counteract the ion transport defect in cystic fibrosis. [source] | ||||||||||