Intragastric pH regulates conversion from net acid to net alkaline secretion by the rat stomach

Coşkun, Tamer; Chu, Shaoyou; Montrose, Marshall H.

doi:10.1152/ajpgi.2001.281.4.g870

Cited by 10 publications

(22 citation statements)

References 34 publications

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“…The pH-stat method thus detects only H ϩ loss or HCO 3 Ϫ increase. Conversely, the CO 2 -sensitive electrode, only measures HCO 3 Ϫ or CO 2 concentrations, which are not confounded by epithelial H ϩ secretion (3,15). The mechanism by which inhibition of NHE3 activity increased DBS, especially by S3226, is not well understood.…”

Section: Discussionmentioning

confidence: 99%

NHE3 inhibition activates duodenal bicarbonate secretion in the rat

Furukawa¹,

Bi²,

Guth³

et al. 2004

American Journal of Physiology-Gastrointestinal and Liver Physi

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We examined the effect of inhibition of Na ϩ /H ϩ exchange (NHE) on duodenal bicarbonate secretion (DBS) in rats to further understand DBS regulation. DBS was measured by using the pH-stat method and by using CO2-sensitive electrodes. 5-(N,N-dimethyl)-amiloride (50 M; DMA), a concentration that selectively inhibits the NHE isoforms NHE1 and NHE2, but not NHE3, did not affect DBS. Nevertheless, 3 mM DMA, a higher concentration that inhibits NHE1, NHE2, and NHE3, significantly increased DBS. Moreover, S1611 and S3226, both specific inhibitors of NHE3 only, or perfusion with Na ϩ -free solutions, dose dependently increased DBS, as measured by pH-stat and CO2-sensitive electrode, without affecting intracellular pH. Coperfusion with 0.1 M indomethacin, 0.5 mM DIDS, or 1 mM methazolamide did not affect S3226-induced DBS. Nevertheless, coperfusion with 0.1 and 0.3 mM 5-nitro-2-(3-phenylpropylamino) benzoic acid, which inhibits the cystic fibrosis transmembrane conductor regulator (CFTR), dose dependently inhibited S3226-induced DBS. In conclusion, only specific apical NHE3 inhibition increased DBS, whereas prostaglandin synthesis, Na ϩ -HCO 3 Ϫ cotransporter activation, or intracellular HCO 3 Ϫ formation by carbonic anhydrase was not involved. Because NHE3 inhibition-increased DBS was inhibited by an anion channel inhibitor and because reciprocal CFTR regulation has been previously shown between NHE3 and apical membrane anion transporters, we speculate that NHE3 inhibition increased DBS by altering anion transporter function. epithelial cells; cystic fibrosis transmembrane conductance regulator; back titration; S3226 DUODENAL EPITHELIAL BICARBONATE secretion (DBS) is one of the most important mechanisms by which the duodenum is protected from the injurious effects of secreted gastric acid (6, 16). DBS is regulated by humoral factors such as PGE 2 , VIP, glucagon, gastric inhibitory peptide, and the enteric nervous system (6). These factors promote cAMP production, which stimulates the cystic fibrosis transmembrane conductor regulator (CFTR), an apical anion channel (19,20), and the basolateral Na ϩ -HCO 3 Ϫ cotransporter (NBC1), an HCO 3 Ϫ uptake pathway (4,22,35). Recently, six Na ϩ /H ϩ exchanger (NHE) isoforms have been cloned. Of these isoforms, NHE1, 2, and 3 are expressed in the intestine of humans, rabbits, and rats (10, 21). In the small intestine, particularly in the duodenum, apical NHE2 and NHE3 are expressed in human, rabbits, rats, and mice (10,21,34). In the colonic surface mucosa, an apical NHE3 plays a key absorptive role for Na ϩ , concomitant with H ϩ excretion (31). In contrast, NHE2 may promote Na ϩ absorption from colonic crypts (12), whereas playing only a minor role in overall small intestinal electrolyte transport (18,29).In a recently published clinical study (36), inhibition of NHE2 and NHE3 by amiloride increased DBS. This increased DBS was thought to result from decreased NHE2-and NHE3-mediated H ϩ secretion into the lumen, increasing the amount of measured titratable alkalinity. Although it...

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Section: Discussionmentioning

confidence: 99%

NHE3 inhibition activates duodenal bicarbonate secretion in the rat

Furukawa¹,

Bi²,

Guth³

et al. 2004

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…The pH of the gastric mucus or the gastric surface is a subject of controversy. Some suggest that the pH is close to neutral, but microelectrode and fluorimetric methods have generally shown a loss of pH regulation in the gastric mucus when the pH falls below 2.0 (14,45). This pH, representing a concentration of 10 mM HCl, is not able to be buffered by the maximal capacity of the stomach to secrete bicarbonate, which is 10% of acid output.…”

mentioning

confidence: 99%

Acid-Adaptive Genes of Helicobacter pylori

Wen

Marcus

Matrubutham³

et al. 2003

Infect Immun

193

278

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Helicobacter pylori is the only neutralophile that has been able to colonize the human stomach by using a variety of acid-adaptive mechanisms. One of the adaptive mechanisms is increased buffering due to expression of an acid-activated inner membrane urea channel, UreI, and a neutral pH-optimum intrabacterial urease. To delineate other possible adaptive mechanisms, changes in gene expression in response to acid exposure were examined using genomic microarrays of H. pylori exposed to different levels of external pH (7.4, 6.2, 5.5, and 4.5) for 30 min in the absence and presence of 5 mM urea. Gene expression was correlated with intrabacterial pH measured using 2,7-bis-(2-carboxyethyl)-5-carboxyfluorescein and compared to that observed with exposure to 42°C for 30 min. Microarrays containing the 1,534 open reading frames of H. pylori strain 26695 were hybridized with cDNAs from control (pH 7.4; labeled with Cy3) and acidic (labeled with Cy5) conditions. The intrabacterial pH was 8.1 at pH 7.4, fell to 5.3 at pH 4.5, and rose to 6.2 with urea. About 200 genes were up-regulated and ϳ100 genes were down-regulated at pH 4.5 in the absence of urea, and about half that number changed in the presence of urea. These genes included pH-homeostatic, transcriptional regulatory, motility, cell envelope, and pathogenicity genes. The up-regulation of some pH-homeostatic genes was confirmed by real-time PCR. There was little overlap with the genes induced by temperature stress. These results suggest that H. pylori has evolved multifaceted acid-adaptive mechanisms enabling it to colonize the stomach that may be novel targets for eliminating infection.

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“…Luminal pH 5. Experiments were performed to quantify pH and chloride secretion simultaneously during stimulated acid secretion.…”

Section: Resultsmentioning

confidence: 99%

“…Omeprazole unmasks bicarbonate secretion without affecting accompanying chloride secretion. In the presence of omeprazole, Coskun et al (5) previously observed that gastric bicarbonate secretion was greater at luminal pH 3 compared with luminal pH 5. In the current report, we observed that Cl Ϫ secretion was also greater at luminal pH 3 compared with luminal pH 5 (compare Figs.…”

Section: Discussionmentioning

confidence: 95%

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Coordinated regulation of gastric chloride secretion with both acid and alkali secretion

Coşkun

Baumgartner

Chu

et al. 2002

American Journal of Physiology-Gastrointestinal and Liver Physi

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. Coordinated regulation of gastric chloride secretion with both acid and alkali secretion Am J Physiol Gastrointest Liver Physiol 283: G1147-G1155, 2002. First published July 17, 2002 10.1152/ajpgi.00184.2002Gastric secretion of hydrochloric acid requires protons and chloride, yet the mechanisms and regulation of gastric chloride secretion remain unclear. We developed an in vivo technique to simultaneously measure acid/base and chloride secretion into the gastric lumen of anesthetized rats. The cannulated stomach lumen was perfused with weakly pH-buffered chloride-free solution containing a chloride-sensitive fluorophore [5 M N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide (MQAE)]. Gastric acid and chloride secretion was detected in gastric effluents by 1) flow-through pH electrode and 2) MQAE fluorescence. Gastric effluent was also collected at 1-min intervals for independent determination of chloride amount by chloridometer. In all conditions, both optical and chemical determinations of chloride report similar amounts of secreted chloride. During luminal perfusion with pH 5 solution, net acid and chloride secretion into the lumen was observed. Pentagastrin stimulated both secretions. In contrast, proton pump inhibition (omeprazole) caused alkalinization of the gastric effluent, but chloride secretion was not diminished. During luminal pH 3 perfusion, net alkali secretion was observed, and chloride secretion at luminal pH 3 was greater than pH 5. When tissue is pretreated with omeprazole at luminal pH 3, the addition of prostaglandin E2 synchronously stimulates both alkali and chloride secretion. Results suggest that both acid and alkali secretions are separately coupled with chloride secretion. proton pump, fluorescence, rat, stomach gastric luminal pH

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Intragastric pH regulates conversion from net acid to net alkaline secretion by the rat stomach

Cited by 10 publications

References 34 publications

NHE3 inhibition activates duodenal bicarbonate secretion in the rat

NHE3 inhibition activates duodenal bicarbonate secretion in the rat

Acid-Adaptive Genes of Helicobacter pylori

Coordinated regulation of gastric chloride secretion with both acid and alkali secretion

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