Mucosal Acidification Research Articles

Saliva Production and Esophageal Motility Influence Esophageal Acid Clearance Related toPost-reflux Swallow-Induced Peristaltic Wave.

The post-reflux swallow-induced peristaltic wave (PSPW) brings salivary bicarbonate to neutralize residual distal esophageal mucosal acidification. To determine if reduced saliva production and esophageal body hypomotility would compromise PSPW-induced pH recovery in the distal esophagus. In this multicenter retrospective cross-sectional study, patients with confirmed Sjogren's syndrome and scleroderma/mixed connective tissue disease (MCTD) who underwent high resolution manometry (HRM) and ambulatory pH-impedance monitoring off antisecretory therapy were retrospectively identified. Patients without these disorders undergoing HRM and pH-impedance monitoring for GERD symptoms were identified from the same time-period. Acid exposure time, numbers of reflux episodes and PSPW, pH recovery with PSPW, and HRM metrics were extracted. Univariate comparisons and multivariable analysis were performed to determine predictors of pH recovery with PSPW. Among Sjogren's syndrome (n = 34), scleroderma/MCTD (n = 14), and comparison patients with reflux symptoms (n = 96), the scleroderma/MCTD group had significantly higher AET, higher prevalence of hypomotility, lower detected reflux episodes, and very low numbers of PSPW (p ≤ 0.004 compared to other groups). There was no difference in pH-impedance metrics between Sjogren's syndrome, and comparison patients (p ≥ 0.481). Proportions with complete pH recovery with PSPW was lower in Sjogren's patients compared to comparison reflux patients (p = 0.009), predominantly in subsets with hypomotility (p < 0.001). On multivariable analysis, diagnosis of Sjogren's syndrome, scleroderma/MCTD or neither (p = 0.014) and esophageal hypomotility (p = 0.024) independently predicted lack of complete pH recovery with PSPW, while higher total reflux episodes trended (p = 0.051). Saliva production and motor function are both important in PSPW related pH recovery.

Mucosal acidosis elicits a unique molecular signature in epithelia and intestinal tissue mediated by GPR31-induced CREB phosphorylation

Metabolic changes associated with tissue inflammation result in significant extracellular acidosis (EA). Within mucosal tissues, intestinal epithelial cells (IEC) have evolved adaptive strategies to cope with EA through the up-regulation of SLC26A3 to promote pH homeostasis. We hypothesized that EA significantly alters IEC gene expression as an adaptive mechanism to counteract inflammation. Using an unbiased RNA sequencing approach, we defined the impact of EA on IEC gene expression to define molecular mechanisms by which IEC respond to EA. This approach identified a unique gene signature enriched in cyclic AMP response element-binding protein (CREB)-regulated gene targets. Utilizing loss- and gain-of-function approaches in cultured epithelia and murine colonoids, we demonstrate that EA elicits prominent CREB phosphorylation through cyclic AMP-independent mechanisms that requires elements of the mitogen-activated protein kinase signaling pathway. Further analysis revealed that EA signals through the G protein-coupled receptor GPR31 to promote induction of FosB, NR4A1, and DUSP1. These studies were extended to an in vivo murine model in conjunction with colonization of a pH reporter Escherichia coli strain that demonstrated significant mucosal acidification in the TNFΔARE model of murine ileitis. Herein, we observed a strong correlation between the expression of acidosis-associated genes with bacterial reporter sfGFP intensity in the distal ileum. Finally, the expression of this unique EA-associated gene signature was increased during active inflammation in patients with Crohn's disease but not in the patient control samples. These findings establish a mechanism for EA-induced signals during inflammation-associated acidosis in both murine and human ileitis.

Insights into the impact of inflammatory acidification on the mucosa

Mucosal acidification is an often-underappreciated aspect of mucosal inflammation. Like other chronic inflammatory diseases, tissue acidification has been observed in inflammatory bowel disease (IBD) patients, with reports of colonic pH as low as 4. We recently demonstrated that neutrophil (PMN) transepithelial migration rapidly acidifies the microenvironment resulting in inflammatory acidification of the mucosa. Furthermore, we identified an adaptive tissue response in IEC which buffered extracellular acidification during PMN transepithelial migration, suggesting pH homeostasis is important during acute inflammation. Very little is known in regard to the impact of extracellular acidification on the intestinal epithelial cell (IEC) function. To better understand the impact of extracellular pH on IEC cell function, we investigated the impact of extracellular acidosis on IEC gene expression. Guided by an unbiased RNAseq of T84 IEC exposed to low pH, we identified significant induction of several CREB associated genes. Based on this observation, we examined the phosphorylation of CREB under acidic conditions. Under acidic conditions, CREB is rapidly phosphorylated. We observed CREB phosphorylation within 5 minutes of exposure to acidic conditions and peaks at 30 min. Extending these studies we investigated the mechanism(s) involved in acidosis induced CREB phosphorylation. Interestingly, cAMP signaling, a common signaling pathway for CREB phosphorylation, appears to not be involved in acidosis-induced CREB phosphorylation. Under acidic conditions, there was no significant increase in cAMP levels in IEC and acidosis-induced CREB phosphorylation was still observed in T84 IEC treated with cAMP inhibitors. KEGG analysis of the RNAseq data revealed the induction of several MAPK regulatory genes, including members of the NR4A and DUSP families. Based on this observation we examined several key proteins involved in MAPK signaling, ERK1/2 and MSK1. Under acidic conditions ERK1/2 and MSK1 are rapidly phosphorylation and treatment with a MEK1/2 or MSK1 inhibitor significant attenuated CREB phosphorylation under acidic conditions. Further examination revealed CREB phosphorylation signals through the GaI-linked GPCR, GRP31. Finally, we extended our studies in vivo and examined mucosal acidification in a murine model of ileitis, TNFΔARE mice. Using a novel pH reporting E. coli strain, we identified significant mucosal acidification in the distal ileum of TNFΔARE mice when compared to WT mice. Mucosal acidification was positively correlated with the expression of several acidification associated genes; FosB, NR4A1, and CXCL1. These results identify extracellular acidification as a significant signaling mechanism during tissue inflammation. Thus, regulation of GPR31 or MSK1 may serve as new therapeutic targets to limit acidosis signaling during mucosal inflammation.

Roles of Up-Regulated Expression of ASIC3 in Sex Difference of Acid-Induced Duodenal HCO3 - Responses.

Although the morbidity of ulcers is statistically higher in males than females, the mechanism of this difference remains unknown. Recent studies show that duodenal HCO3 - response to mucosal acidification is higher in females than males, and this may be a factor responsible for the sex difference in the mucosal protective mechanisms. In this article, we examined the duodenal HCO3 - responses to various stimuli in male and female rats, including estrogen, and reviewed the mechanisms responsible for the sex difference in the acid-induced HCO3 - secretion. Mucosal acidification was performed by exposing the duodenum to 10 mM HCl for 10 min. PGE2 was administered intravenously, while capsaicin was applied topically to the duodenum for 10 min. Tamoxifen was given s.c. 30 min before the acidification. Ovariectomy was performed 2 weeks before the experiments; half of the animals were given estrogen i.m. after the operation. Mucosal acidification increased duodenal HCO3 - secretion in male rats, and this response was inhibited by indomethacin and sensory deafferentation. Although no sex difference was found in HCO3 - responses to PGE2 and capsaicin, the response to acid was significantly greater in female than male rats. The different HCO3 - response to acid disappeared on ovariectomy, and this effect was totally reversed by the repeated administration of estrogen. The gene expression of ASIC3 in female rats was greater than in male rats and down-regulated by ovariectomy or tamoxifen treatment in an estradiol- dependent manner, while no sex difference was observed in TRPV1 and CFTR expressions. In conclusion, the acid-induced HCO3 - response is greater in female than male rats, and this phenomenon is not due to changes in PGE2 sensitivity or TRPV1/CFTR expressions but may be accounted for by increased expression of ASIC3 on sensory neurons, which is associated with the chronic influence of estrogen.

CrossTalk opposing view: mucosal acidification does not drive early progressive lung disease in cystic fibrosis.

CrossTalk opposing view: mucosal acidification does not drive early progressive lung disease in cystic fibrosis.

CrossTalk proposal: mucosal acidification drives early progressive lung disease in cystic fibrosis.

CrossTalk proposal: mucosal acidification drives early progressive lung disease in cystic fibrosis.

Effects of dissolved carbon dioxide on the integrity of the rumen epithelium: An agent in the development of ruminal acidosis.

The carbon dioxide released and dissolved in rumen fluid may easily permeate across the epithelial cell membrane. Thus, we hypothesized that CO2 may act as proton carrier and induce epithelial damage under acidotic conditions. Ovine ruminal epithelia were mounted in Ussing chambers under short-circuit conditions. The serosal buffer solution had a constant pH of 7.4 and was gassed either with 100% oxygen or with carbogen (95% O2 /5% CO2 ). The mucosal solution was gassed with either 100% oxygen or 100% carbon dioxide. The mucosal pH was lowered stepwise from 6.6 to 5.0 in the presence or absence of short-chain fatty acids (SCFA). The transepithelial conductance (Gt ) as an indicator of epithelial integrity and the short-circuit current (Isc ) as an indicator of active electrogenic ion transfer were continuously monitored. At an initial mucosal pH of 6.6, there was no significant difference in Gt between the treatment groups. In the absence of both SCFA and CO2 , Gt remained constant when the mucosal solution was acidified to pH 5.0. In the presence of SCFA, mucosal acidification induced a significant rise in Gt when the solutions were gassed with oxygen. A small increase in Gt was observed in the mucosal presence of CO2 . However, no difference in final Gt was observed between SCFA-containing and SCFA-free conditions under carbon dioxide gassing during stepwise mucosal acidification. The SCFA+proton-induced increase in Gt could also be minimized by serosal gassing with carbogen. Because of the SCFA+proton-induced changes in Gt and their attenuation by CO2 , a protective role for mucosally available carbon dioxide may be assumed. We suggest that this effect may be due to the intraepithelial conversion of carbon dioxide to bicarbonate. However, the serosal presence of CO2 at a physiological concentration may be sufficient to protect the epithelia from SCFA+proton-induced damage for a certain period of time.

Effect of sodium hydrosulfide on mRNA expression of prostaglandin E2 receptors in response to mucosal acidification and distention-induced gastric acid secretion in rats.

Objective(s):Prostaglandins have been shown to mediate the gastro-protective effect of sodium hydrosulfide (NaHS) but effect of NaHS on mRNA expression of prostaglandin E2 receptors (EP1, 3-4; EPs) has not been investigated. Therefore, this study designed to evaluate the effect of NaHS on mRNA expression of EPs receptors in response to mucosal acidification and distention-induced gastric acid secretion in rats.Materials and Methods:Fasted rats were randomly assigned into 4 groups (n=6/group). They were control, and NaHS-treated groups. To evaluate the effect of NaHS on mucosal mRNA expression of EPs receptors, the gastric mucosa exposed to stimulated gastric acid output and mucosal acidification. The pylorus sphincter catheterized for instillation of isotonic neutral saline or acidic solution. Ninety min after beginning the experiments, animals sacrificed and the gastric mucosa collected to determine the pH, mucus secretion and to quantify the mRNA expression of EPs receptors by quantitative real-time PCR.Results:present results showed that a) NaHS increased the mucus secretion, mRNA expression of EP3 and EP4 receptors in response to distention-induced expression; b) The mRNA expression of EP1 receptors increased while EP4 mRNA receptors decreased in response to mucosal acidification in NaHS-pretreated rats; and c) NaHS increased pH of gastric contents both in response to distention-induced gastric acid secretion and mucosal acidification.Conclusion:NaHS behaves in a different manner. It effectively only increased the pH of gastric contents to reinforce the gastric mucosa against a highly acidic solution but modulated both acid and mucus secretion when the rate of acid increase in the stomach was slower.

Probiotics in management of hepatic encephalopathy.

Gut microflora leads to production of ammonia and endotoxins which play important role in the pathogenesis of hepatic encephalopathy (HE). There is relationship between HE and absorption of nitrogenous substances from the intestines. Probiotics play a role in treatment of HE by causing alterations in gut flora by decreasing the counts of pathogen bacteria, intestinal mucosal acidification, decrease in production and absorption of ammonia, alterations in permeability of gut, decreased endotoxin levels and changes in production of short chain fatty acids. Role of gut microbiota using prebiotics, probiotics and synbiotics have been evaluated in the management of minimal hepatic encephalopathy (MHE), overt HE and prevention of HE. Many studies have shown efficacy of probiotics in reduction of blood ammonia levels, treatment of MHE and prevention of HE. However these trials have problems like inclusion of small number of patients, short treatment durations, variability in HE/MHE related outcomes utilized and high bias risk, errors of systematic and random types. Systematic reviews also have shown different results with one systematic review showing clinical benefits whereas another concluded that probiotics do not have any role in treatment of MHE or HE. Also practical questions on optimal dose, ideal combination of organisms, and duration of treatment and persistence of benefits on long term follow-up are still to be clarified. At present, there are no recommendations for use of probiotics in patients with HE.

Mucosal acidification increases hydrogen sulfide release through up-regulating gene and protein expressions of cystathionine gamma-lyase in the rat gastric mucosa.

This study was performed to investigate the effects of mucosal acidification on mRNA expression and protein synthesis of cystathionine gamma lyase (CSE), cystathionine beta synthase (CBS), and mucosal release of H2S in gastric mucosa in rats. Thirty-two rats were randomly assigned into 4 groups (8 in each), including: the control group, HCl (10 mM) treated group, HCl (100 mM) treated group, and one group to study the effect of Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME). Anesthetized rats underwent tracheostomy and midline laparotomy. Ninety min after the instillation of neutral or acidic solutions, animals were sacrificed and the gastric mucosa was collected to measure the H2S concentration by ELISA method and to quantify mRNA expression of CSE and CBS by quantitative real-time PCR (qRT-PCR). Protein synthesis was also detected by Western blot method. Mucosal acidification with 10 and 100 HCl, significantly increased mucosal levels of H2S (P<0.01 and P<0.001) and mRNA (P<0.01 and P<0.001) and protein expressions of CSE (P<0.01 and P<0.001). L-NAME treatment reversed H2S release to control level. Our findings indicated that mucosal acidification with HCl increased mucosal release of H2S through upregulation of CSE gene and its protein expression. This effect is mainly mediated through the involvement of nitric oxide.

H2S-induced HCO3− secretion in the rat stomach – Involvement of nitric oxide, prostaglandins, and capsaicin-sensitive sensory neurons

Hydrogen sulfide (H2S) is known to be an important gaseous mediator that affects various functions under physiological and pathological conditions. We examined the effects of NaHS, a H2S donor, on HCO3− secretion in rat stomachs and investigated the mechanism involved in this response. Under urethane anesthesia, rat stomachs were mounted on an ex vivo chamber and perfused with saline. Acid secretion had been inhibited by omeprazole. The secretion of HCO3− was measured at pH 7.0 using a pH-stat method and by the addition of 10 mM HCl. NaHS (0.5–10 mM) was perfused in the stomach for 5 min. Indomethacin or L-NAME was administered s.c. before NaHS treatment, while glibenclamide (a KATP channel blocker), ONO-8711 (an EP1 antagonist), or propargylglycine (a cystathionine γ-lyase inhibitor) was given i.p. before. The mucosal perfusion of NaHS dose-dependently increased the secretion of HCO3−, and this effect was significantly attenuated by indomethacin, L-NAME, and sensory deafferentation, but not by glibenclamide or ONO-8711. The luminal output of nitric oxide, but not the mucosal production of prostaglandin E2, was increased by the perfusion of NaHS. Mucosal acidification stimulated HCO3− secretion, and this response was inhibited by sensory deafferentation, indomethacin, L-NAME, and ONO-8711, but not by propargylglycine. These results suggested that H2S increased HCO3− secretion in the stomach, and this effect was mediated by capsaicin-sensitive afferent neurons and dependent on nitric oxide and prostaglandins, but not ATP-sensitive K+ channels. Further study is needed to define the role of endogenous H2S in the mechanism underlying acid-induced gastric HCO3− secretion.

S6-4 Stimulation of duodenal HCO3− secretion by H2S in rats: Regulatory mechanism and importance in mucosal defense

We examined the effect of H2S on duodenal HCO 3 - secretion in rats and investigated the mechanism involved in this response. Animals were fasted overnight and anesthetized with urethane. A duodenal loop was perfused with saline, and HCO 3 - secretion was measured at pH 7.0 using a pH stat-method. The loop was perfused at a rate of 0.2 mL/min with NaHS (H2S donor) for 5 min or 10 mM HCl for 10 min. Indomethacin or l -NAME was given s.c. 30 min or 3 h, respectively, before NaHS or acidification, while glibenclamide (KATP channel blocker) or propargylglycine (cystathionine-g-lyase inhibitor) was given i.p. 30 min before. Mucosal perfusion with NaHS dose-dependently increased the HCO 3 - secretion, and this effect was significantly attenuated by indomethacin and l -NAME as well as sensory deafferentation, but not by glibenclamide. Mucosal PGE2 and NO production were both increased by NaHS perfusion. Mucosal acidification stimulated HCO 3 - secretion concomitant with increase in PGE2 and NO production, and these responses were mitigated by propargylglycine. The duodenal damage induced by acid (100 mM HCl for 4 h) was aggravated by pretreatment with propargylglycine. These results suggest that H2S increases HCO 3 - secretion in the duodenum, and this action is partly mediated by PG and NO as well as by capsaicin-sensitive afferent neurons. It is assumed that endogenous H2S is involved in the regulatory mechanism of acid-induced HCO 3 - secretion and mucosal protection in the duodenum.

Effect of celecoxib, a COX‐2 selective inhibitor, on duodenal HCO3‐ and ulcereogenic responses caused by mucosal acidification in rats (904.3)

We examined the effect of celecoxib, a selective COX‐2 inhibitor, on duodenal HCO3‐ and ulcerogenic responses caused by acid in rats, in comparison with indomethacin and loxoprofen (nonselective COX inhibitors) or SC‐560 (a selective COX‐1 inhibitor). Methods: Male SD rats were used after 18 h fasting. Under urethane anesthesia, the duodenal loop was perfused with saline, and the HCO3‐ secretion was measured at pH 7.0 using a pH‐stat method. Results: Mucosal acidification (exposure to 10 mM HCl for 10 min) stimulated HCO3‐ secretion with an increase of mucosal PGE2 contents in the duodenum. These responses were significantly attenuated by pretreatment with indomethacin, loxoprofen or SC‐560, while celecoxib had no effect. Perfusion of the loop with 100 mM HCl for 4 h produced mild hemorrhagic damage, and the severity of these lesions was significantly aggravated by indomethacin, loxoprofen and SC‐560 but not celecoxib. COX‐2 was not expressed in the duodenal mucosa after acidification, while COX‐1 was expressed in the normal mucosa and remained unchanged after acid treatment. Conclusion: These results confirmed the importance of COX‐1 in the mechanism for the acid‐induced duodenal HCO3‐ secretion and further suggested that COX‐1/PGs play a crucial role in the protection of the duodenal mucosa against acid injury.

Gender Difference in Duodenal HCO3‐ Response to Mucosal Acidification: Importance of Up‐regulation of ASIC3 by Estradiol

In the present study, we investigated the mechanism responsible for the gender difference in the acid‐induced duodenal HCO3‐ secretion. Male and female SD rats were used after 18 h fasting. Under urethane anesthesia, a proximal duodenal loop was perfused with saline, and HCO3‐ secretion was measured. Mmucosal acidification was performed by exposing the loop to 10 mM HCl for 10 min. Ovariectomy was performed 2 weeks before the experiments, and 17β‐estradiol was given i.m. on day 3, 7 and 10 after the operation. Although no difference was found in the HCO3‐ responses to PGE2 and capsaicin between male and female rats, the response to acid was significantly greater in female rats. However, this different response to acid was dissipated by ovariectomy, and this effect was antagonized by the repeated estradiol treatment. The expression of ASIC3 mRNA was greater in female rats and down‐regulated by ovariectomy, in an estradiol‐dependent manner. These results suggest that the acid induced‐HCO3‐ secretion was greater in female than male rats, and the mechanism for the different response may be accounted for by the up‐regulation of ASIC3 expression in female rats.

1118 Gender Difference in Duodenal HCO3- Response to Mucosal Acidification: Importance of Up-Regulation of ASIC3 by Estradiol

1118 Gender Difference in Duodenal HCO3- Response to Mucosal Acidification: Importance of Up-Regulation of ASIC3 by Estradiol

Gas Mediators Involved in Modulating Duodenal HCO3- Secretion

The secretion of HCO3(-) in the duodenum is increased by mucosal acidification, and this process is modulated by gas mediators such as nitric oxide (NO), hydrogen sulfide (H2S), and carbon monoxide (CO), in addition to prostaglandins (PGs). The secretion is increased by NOR3 (NO donor), NaHS (H2S donor), and CORM-2 (CO donor). The HCO3(-) responses to NOR3 and CORM-2 are attenuated by indomethacin, while that to NaHS is mitigated by indomethacin and L-NAME as well as sensory deafferentation. NOR3 and CORM-2 increase mucosal PGE2 production, while H2S increases mucosal PGE2 content and luminal NO release. The HCO3(-) response to mucosal acidification is attenuated by indomethacin, propargylglycine, and SnPP, each inhibiting PG, H2S and CO production, respectively. The acid-induced duodenal damage is worsened when either PG, H2S or CO is lacking. These findings suggest that 1) NO, H2S, and CO, generated endogenously or exogenously, stimulate HCO3(-) secretion in the duodenum; 2) the stimulatory action of NO and CO is mediated, at least partly, by endogenous PGs, while that of H2S is mediated by PGs and NO as well as sensory neurons; 3) these gas mediators are involved in the local regulation of acid-induced HCO3(-) secretion, in addition to endogenous PGs; 4) the acid-induced duodenal damage is worsened by agents inhibiting the endogenous production of NO, H2S or CO. It is assumed that these gas mediators play a role in maintaining the integrity of the duodenal mucosa by modulating the secretion of HCO3(-).

Stimulation of duodenal HCO3− secretion by hydrogen sulphide in rats: relation to prostaglandins, nitric oxide and sensory neurones

We examined the effect of H₂S on duodenal HCO₃⁻ secretion in rats and investigated the mechanism involved in this response. Animals were fasted for 18 h and anaesthetized with urethane. A duodenal loop was perfused with saline, and HCO₃⁻ secretion was measured at pH 7.0 using a pH stat-method. The loop was perfused at a rate of 0.2 mL min⁻¹ with NaHS (H₂S donor: 0.1-1 mm) for 5 min or 10 mm HCl for 10 min. Indomethacin or l-NAME [nitric oxide (NO) synthase inhibitor) was given s.c. 30 min or 3 h, respectively, before NaHS or acidification, while glibenclamide (K(ATP) channel blocker) or propargylglycine (cystathionine-g-lyase inhibitor) was given i.p. 30 min before. Mucosal perfusion with NaHS dose dependently increased the HCO₃⁻ secretion, and this effect was significantly attenuated by indomethacin and l-NAME as well as by sensory deafferentation, but not by glibenclamide. Mucosal prostaglandin E₂ (PGE₂) production and luminal release of NO were both increased by NaHS perfusion. Mucosal acidification stimulated HCO₃⁻ secretion concomitant with an increase in PGE₂ and NO production, and these responses were mitigated by propargylglycine. The duodenal damage induced by acid (100 mm HCl for 4 h) was aggravated by pre-treatment with propargylglycine. These results suggest that H₂S increases HCO₃⁻ secretion in the rat duodenum, and that this action is partly mediated by PG and NO as well as by capsaicin-sensitive afferent neurones. It is assumed that endogenous H₂S is involved in the regulatory mechanism of acid-induced HCO₃⁻ secretion and mucosal protection in the duodenum.

Prostaglandin EP Receptor Subtypes Involved in Regulating HCO3- Secretion from Gastroduodenal Mucosa

Gastroduodenal HCO(3)(-) secretion is a key process that aids in preventing acid-peptic injury. The HCO(3)(-) secretion in rats and mice was increased in response to PGE(2) as well as mucosal acidification, the latter response occurring with a concomitant enhancement of mucosal PG production. The duodenal responses to PGE(2) and acid were decreased in mice lacking EP3 receptors and reduced by coadministration of an EP3 or EP4 antagonist in rats, complete inhibition being observed when the EP3 and EP4 antagonists were given together. By contrast, the gastric responses disappeared in EP1-knockout mice and were prevented by an EP1 antagonist but not other EP antagonists. Furthermore, duodenal HCO(3)(-) secretion was stimulated by the EP3 and EP4 agonists, whereas gastric HCO(3)(-) secretion was increased only by the EP1 agonist. In addition, the HCO(3)(-) stimulatory effect of sulprostone (an EP1/EP3 agonist) in the duodenum was inhibited by verapamil, a Ca(2+) antagonist, and enhanced by isobutyl- methylxanthine, a phosphodiesterase (PDE) inhibitor, but the response in the stomach was inhibited by verapamil and not affected by isobutylmethylxanthine. In the mouse duodenum but not stomach, the response to PGE(2) was potentiated by both vinpocetine (a PDE1 inhibitor) and cilostamide (a PDE3 inhibitor). These results suggest that the HCO(3)(-) stimulatory effect of PGE(2) in the duodenum is mediated by both EP3 and EP4 receptors, being coupled intracellularly with Ca(2+) and cAMP, while that in the stomach is mediated by EP1 receptors, coupled with Ca(2+). In addition, both PDE1 and PDE3 are involved in the regulation of duodenal HCO(3)(-) secretion.

Oesophageal shortening: in vivo validation of high-frequency ultrasound measurements of oesophageal muscle wall thickness

Background and aimsAssessment of oesophageal muscle wall thickness with high-frequency intraluminal ultrasound (HFIUS) is proposed as a method to evaluate longitudinal muscle contraction and oesophageal shortening in patients with oesophageal...

789 Gender Difference in Duodenal HCO3- Response to Mucosal Acidification in Rats: Importance of Up-Regulation of ASIC3 By Estradiol

789 Gender Difference in Duodenal HCO3- Response to Mucosal Acidification in Rats: Importance of Up-Regulation of ASIC3 By Estradiol