Gastroduodenal Bicarbonate Secretion

Seidler, Ursula; Sjöblom, Markus

doi:10.1016/b978-0-12-382026-6.00048-8

Cited by 15 publications

(22 citation statements)

References 332 publications

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“…Isenberg et al showed in 1987 that patients with duodenal ulcer disease have a depressed basal secretory rate and a markedly reduced secretory response to luminal acid [30]. The mechanisms by which this secretion is regulated have been studied in detail over a long period of time, but novel findings are still made that are important for understanding how this secretion is controlled [31]. In the present study, we showed that NPS significantly decreased the basal bicarbonate secretory rate.…”

Section: Discussionsupporting

confidence: 54%

Neuropeptide S reduces duodenal bicarbonate secretion and ethanol-induced increases in duodenal motility in rats

Saudi

Sjöblom

2017

PLoS ONE

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Alcohol disrupts the intestinal mucosal barrier by inducing metabolic and functional changes in epithelial cells. Recently, we showed that neuropeptide S (NPS) decreases duodenal motility and increases mucosal paracellular permeability, suggesting a role of NPS in the pathogenesis of disorders and dysfunctions in the small intestine. The aim of the present study was to investigate the effects of NPS on ethanol- and HCl-induced changes of duodenal mucosal barrier function and motility. Rats were anaesthetized with thiobarbiturate, and a 30-mm segment of the proximal duodenum with an intact blood supply was perfused in situ. The effects on duodenal bicarbonate secretion, the blood-to-lumen clearance of 51Cr-EDTA, motility and transepithelial net fluid flux were investigated. Intravenous (i.v.) administration of NPS significantly reduced duodenal mucosal bicarbonate secretion and stimulated mucosal transepithelial fluid absorption, mechanisms dependent on nitrergic signaling. NPS dose-dependently reduced ethanol-induced increases in duodenal motility. NPS (83 pmol·kg-1·min-1, i.v.) reduced the bicarbonate and fluid secretory response to luminal ethanol, whereas a 10-fold higher dose stimulated fluid secretion but did not influence bicarbonate secretion. In NPS-treated animals, duodenal perfusion of acid (pH 3) induced greater bicarbonate secretory rates than in controls. Pre-treating animals with Nω-nitro-L-arginine methyl ester (L-NAME) inhibited the effect of NPS on bicarbonate secretion. In response to luminal acid, NPS-treated animals had significantly higher paracellular permeability compared to controls, an effect that was abolished by L-NAME. Our findings demonstrate that NPS reduces basal and ethanol-induced increases in duodenal motility. In addition, NPS increases luminal alkalinization and mucosal permeability in response to luminal acid via mechanisms that are dependent on nitric oxide signaling. The data support a role for NPS in neurohumoral regulation of duodenal mucosal barrier function and motility.

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Section: Discussionsupporting

confidence: 54%

Neuropeptide S reduces duodenal bicarbonate secretion and ethanol-induced increases in duodenal motility in rats

Saudi

Sjöblom

2017

PLoS ONE

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“…Duodenal mucosal bicarbonate (HCO 3 − ) secretion (DBS) is considered to be one of the most important defence mechanisms against gastric acid by maintaining an alkaline microclimate near the apical epithelial membrane (Allen & Flemstrom, 2005; Kaunitz & Akiba, 2006; Seidler & Sjöblom, 2012). Different agonists were found to differentially regulate the electrogenic (presumably anion channel dependent) and electroneutral (presumably Cl − /HCO 3 − exchanger‐dependent) HCO 3 − transport pathways (Allen & Flemström, 2005; Seidler & Sjöblom, 2012).…”

Section: Introductionmentioning

confidence: 99%

“…Contact of the duodenal mucosa with acid in the lumen stimulates DBS‐R in all species tested, including humans (Allen & Flemström, 2005; Seidler & Sjöblom, 2012). This acid‐induced DBS‐R involves stimulation of neural circuits (Takeuchi et al 1991; Singh et al 2012), and can therefore only be tested in vivo .…”

Section: Introductionmentioning

confidence: 99%

Molecular transport machinery involved in orchestrating luminal acid‐induced duodenal bicarbonate secretion in vivo

Singh¹,

Liu²,

Riederer³

et al. 2013

The Journal of Physiology

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Key points• Acid damage of the proximal duodenum is a key pathogenic factor in duodenal ulcer disease as well as in the intestinal manifestations of cystic fibrosis.• Short contact of healthy duodenal mucosa with acid results in long-lasting stimulation of proximal duodenal bicarbonate secretion.• While the complex neural, paracrine, humoral and luminocrine regulation of this acid-induced bicarbonate secretory response, as well as its protective role, has been studied in some detail, little is known about the molecular identity of the involved ion transporters or intracellular signalling.• Using genetically engineered mouse models, we found that the anion exchanger DRA (Slc26a3), the anion conductances Slc26a9 and cystic fibrosis transmembrane conductance regulator, and the Na + /H + exchanger isoform 3 play essential roles in orchestrating the acid-induced duodenal bicarbonate secretory response. These transporters are differentially controlled by signalling mechanisms along the crypt-villus axis.• These findings provide a better understanding of the pathophysiology of peptic damage to the duodenum and may provide novel treatment strategies.Abstract The duodenal villus brush border membrane expresses several ion transporters and/or channels, including the solute carrier 26 anion transporters Slc26a3 (DRA) and Slc26a6 (PAT-1), the Na + /H + exchanger isoform 3 (NHE3), as well as the anion channels cystic fibrosis transmembrane conductance regulator (CFTR) and Slc26a9. Using genetically engineered mouse models lacking Scl26a3, Slc26a6, Slc26a9 or Slc9a3 (NHE3), the study was carried out to assess the role of these transporters in mediating the protective duodenal bicarbonate secretory response (DBS-R) to luminal acid; and to compare it to their role in DBS-R elicited by the adenylyl cyclase agonist forskolin. While basal DBS was reduced in the absence of any of the three Slc26 isoforms, the DBS-R to forskolin was not altered. In contrast, the DBS-R to a 5 min exposure to luminal acid (pH 2.5) was strongly reduced in the absence of Slc26a3 or Slc26a9, but not Slc26a6. CFTR inhibitor [CFTR(Inh)-172] reduced the first phase of the acid-induced DBS-R, while NHE3 inhibition (or knockout) abolished the sustained phase of the DBS-R. Luminal acid exposure resulted in the activation of multiple intracellular signalling pathways, including SPAK, AKT and p38 phosphorylation. It induced a biphasic trafficking of NHE3, first rapidly into the brush border membrane, followed by endocytosis in the later stage. We conclude that the long-lasting

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“…Another major component of the human small intestine is bicarbonate, which is secreted by the pancreas as well as the small intestinal epithelial cells. Bicarbonate acts as a pH buffer to neutralize acids secreted by the stomach (61,62). Bicarbonate has also been implicated in virulence gene regulation in V. cholerae (63).…”

Section: Fig 7 V Cholerae Strains Containing a Transcriptional Fusiomentioning

confidence: 99%

Bile Acids and Bicarbonate Inversely Regulate Intracellular Cyclic di-GMP in Vibrio cholerae

Koestler

Waters

2014

Infect Immun

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Vibrio cholerae is a Gram-negative bacterium that persists in aquatic reservoirs and causes the diarrheal disease cholera upon entry into a human host. V. cholerae employs the second messenger molecule 3=,5=-cyclic diguanylic acid (c-di-GMP) to transition between these two distinct lifestyles. c-di-GMP is synthesized by diguanylate cyclase (DGC) enzymes and hydrolyzed by phosphodiesterase (PDE) enzymes. Bacteria typically encode many different DGCs and PDEs within their genomes. Presumably, each enzyme senses and responds to cognate environmental cues by alteration of enzymatic activity. c-di-GMP represses the expression of virulence factors in V. cholerae, and it is predicted that the intracellular concentration of c-di-GMP is low during infection. Contrary to this model, we found that bile acids, a prevalent constituent of the human proximal small intestine, increase intracellular c-di-GMP in V. cholerae. We identified four c-di-GMP turnover enzymes that contribute to increased intracellular c-di-GMP in the presence of bile acids, and deletion of these enzymes eliminates the bile induction of c-di-GMP and biofilm formation. Furthermore, this bile-mediated increase in c-di-GMP is quenched by bicarbonate, the intestinal pH buffer secreted by intestinal epithelial cells. Our results lead us to propose that V. cholerae senses distinct microenvironments within the small intestine using bile and bicarbonate as chemical cues and responds by modulating the intracellular concentration of c-di-GMP.

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Gastroduodenal Bicarbonate Secretion

Cited by 15 publications

References 332 publications

Neuropeptide S reduces duodenal bicarbonate secretion and ethanol-induced increases in duodenal motility in rats

Neuropeptide S reduces duodenal bicarbonate secretion and ethanol-induced increases in duodenal motility in rats

Molecular transport machinery involved in orchestrating luminal acid‐induced duodenal bicarbonate secretion in vivo

Bile Acids and Bicarbonate Inversely Regulate Intracellular Cyclic di-GMP in Vibrio cholerae

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