Evaluation of the efficacy and safety of endoscopic band ligation in the treatment of bleeding from mild to moderate gastric varices type 1.

BACKGROUND: According to practice guidelines, endoscopic band ligation (EBL) and endoscopic tissue adhesive injection (TAI) are recommended for treating bleeding from esophagogastric varices. However, EBL and TAI are known to cause serious complications, such as hemorrhage from dislodged ligature rings caused by EBL and hemorrhage from operation-related ulcers resulting from TAI. However, the optimal therapy for mild to moderate type 1 gastric variceal hemorrhage (GOV1) has not been determined. Therefore, the aim of this study was to discover an individualized treatment for mild to moderate GOV1. AIM: To compare the efficacy, safety and costs of EBL and TAI for the treatment of mild and moderate GOV1. METHODS: A clinical analysis of the data retrieved from patients with mild or moderate GOV1 gastric varices who were treated under endoscopy was also conducted. Patients were allocated to an EBL group or an endoscopic TAI group. The differences in the incidence of varicose relief, operative time, operation success rate, mortality rate within 6 wk, rebleeding rate, 6-wk operation-related ulcer healing rate, complication rate and average operation cost were compared between the two groups of patients. RESULTS: The total effective rate of the two treatments was similar, but the efficacy of EBL (66.7%) was markedly better than that of TAI (39.2%) (P < 0.05). The operation success rate in both groups was 100%, and the 6-wk mortality rate in both groups was 0%. The average operative time (26 min) in the EBL group was significantly shorter than that in the TAI group (46 min) (P < 0.01). The rate of delayed postoperative rebleeding in the EBL group was significantly lower than that in the TAI group (11.8% vs 45.1%) (P < 0.01). At 6 wk after the operation, the healing rate of operation-related ulcers in the EBL group was 80.4%, which was significantly greater than that in the TAI group (35.3%) (P < 0.01). The incidence of postoperative complications in the two groups was similar. The average cost and other related economic factors were greater for the EBL than for the TAI (P < 0.01). CONCLUSION: For mild to moderate GOV1, patients with EBL had a greater one-time varix eradication rate, a greater 6-wk operation-related ulcer healing rate, a lower delayed rebleeding rate and a lower cost than patients with TAI.

Pancreatic pseudoaneurysm mimicking pancreatic tumor: A case report and review of literature.

BACKGROUND: Pancreatic pseudoaneurysm is a rare vascular complication of chronic pancreatitis (CP) or necrotizing pancreatitis with an incidence of 4% to 17%, but it is potentially life-threatening. It is well known that most pancreatic pseudoaneurysms are clinically associated with pancreatic pseudocysts and are usually in the peripancreatic body-tail. A minority of intrapancreatic pseudoaneurysms occur in the absence of pseudocyst formation. Noninvasive computed tomography (CT) and magnetic resonance imaging (MRI) are most commonly used examinations for screening pancreatic pseudoaneurysms. Notably, the rare intrapancreatic pseudoaneurysm in the pancreatic head can mimic a hypervascular solid mass and be misdiagnosed as a pancreatic tumor. CASE SUMMARY: We report the case of a 67-year-old man who had been admitted to our hospital due to recurrent abdominal pain for 1 mo that was aggravated for 5 d. CT and MRI revealed a mass in the pancreatic head with significant expansion of the main pancreatic duct and mild atrophy of the pancreatic body-tail. He was admitted to the department of hepatobiliary and pancreatic surgery due to the possibility of a pancreatic tumor. The patient was then referred for endoscopic ultrasonography (EUS) with possible EUS-FNA. However, EUS showed a cystic lesion in the pancreatic head with wall thickness and enhancing nodules, which was doubtful because it was inconsistent with the imaging findings. Subsequently, color doppler flow imaging demonstrated turbulent arterial blood flow in the cystic lesion and connection with the surrounding vessel. Therefore, we highly suspected the possibility of CP complicated with intrapancreatic pseudoaneurysm, combined with the patient's long-term drinking history and the sonographic features of CP. Indeed, angiography revealed an oval area of contrast medium extravasation (size: 1.0 cm × 1.5 cm) at the far-end branch of the superior pancreaticoduodenal artery, and angiographic embolization was given immediately at the same time. CONCLUSION: EUS is an important differential diagnostic tool when pancreatic pseudoaneurysm mimics the imaging appearance of a hypervascular pancreatic tumor.

Easily misdiagnosed complex Klippel-Trenaunay syndrome: A case report.

BACKGROUND: Klippel-Trenaunay syndrome (KTS) is a congenital vascular malformation with a complicated etiology. It is sporadic and clinically rare in occurrence. The typical characteristics are capillary malformation (also known as port-wine stain), varicose veins and malformations, and bony and/or soft tissue hypertrophy with or without lymphatic malformation, which are known as the "classic clinical triad". Herein, a rare case of KTS characterized by crossed-bilateral limb hypertrophy accompanied by intermittent hematochezia and hematuria is reported. CASE SUMMARY: We described a 37-year-old female with KTS. She was admitted to our hospital owing to the gradual enlargement of the left lower extremity along with intermittent hematochezia and hematuria. The patient was diagnosed to have hemorrhoid bleeding by other hospitals and treated with conventional hemostatic drugs, but continued to have intermittent gastrointestinal bleeding and hematuria. Therefore, she visited our hospital to seek further treatment. During hospitalization, relevant imaging and laboratory examinations and colonoscopy were performed. In combination with the patient's history and relevant examinations, we considered that the patient had a complex form of KTS. We recommended a combined diagnosis and treatment from the vascular, interventional, anorectal, and other departments, although she declined any further treatment for financial reasons. CONCLUSION: The clinical manifestations of KTS are extensive and diverse and chiefly include the typical triad. However, Vascular malformations of KTS can also involve several parts and systems such as digestive and urogenital systems. Therefore, the atypical manifestations and rare complications necessitate the clinician's attention and are not to be ignored.

Synchronous early gastric and intestinal mucosa-associated lymphoid tissue lymphoma in a Helicobacter pylori-negative patient: A case report.

BACKGROUND: Mucosa-associated lymphoid tissue (MALT) lymphoma occurs largely in the digestive tract, with the stomach being the most commonly affected organ, followed by the small intestine, large intestine, and esophagus. It is rarely found in both the stomach and colon. Helicobacter pylori (H. pylori) infection is strongly associated with gastric MALT lymphoma, although there is a small number of H. pylori-negative gastric MALT lymphomas. Diagnosis of MALT lymphoma is challenging because of nonspecific symptoms and diverse presentations of endoscopic findings. CASE SUMMARY: We report a case of an asymptomatic patient who during screening endoscopy and was found to have stromal tumor-like submucosal uplift lesions in the stomach body and polypoid lesions in the rectum. After endoscopic resection, the patient was diagnosed with multiple early simultaneous gastrointestinal MALT lymphomas. CONCLUSION: This study may help improve our understanding of MALT lymphomas and multifocal lesions treated using early endoscopy.

Efficacy of keverprazan for duodenal ulcer: A phase II randomized, double-blind, parallel-controlled trial.

BACKGROUND AND AIM: Considering the limitation of varying acid suppression of proton pump inhibitors, this study was aimed to assess the efficacy, safety, and dose-effect relationship of keverprazan, a novel potassium-competitive acid blocker, in the treatment of duodenal ulcer (DU) compared with lansoprazole. METHODS: A randomized, double-blind, double-dummy, multicenter, low-dose, high-dose, and positive-drug parallel-controlled study was conducted to verify the non-inferiority of keverprazan (20 or 30 mg) to lansoprazole of 30 mg once daily for 4 to 6 weeks and dose-effect relationship of keverprazan in the treatment of patients with active DU confirmed by endoscopy. RESULTS: Of the 180 subjects randomized, including 55 cases in the keverprazan_20 mg group, 61 cases in the keverprazan_30 mg group, and 64 cases in the lansoprazole_30 mg group, 168 subjects (93.33%) completed the study. The proportions of healed DU subjects in the keverprazan_20 mg, keverprazan_30 mg, and lansoprazole_30 mg groups were respectively 87.27%, 90.16%, and 79.69% at week 4 (P = 0.4595) and were respectively 96.36%, 98.36%, and 92.19% at week 6 (P = 0.2577). The incidence of adverse events in the keverprazan_20 mg group was lower than that in the lansoprazole_30 mg (P = 0.0285) and keverprazan_30 mg groups (P = 0.0398). CONCLUSIONS: Keverprazan was effective and non-inferior to lansoprazole in healing DU. Based on the comparable efficacy and safety data, keverprazan of 20 mg once daily is recommended for the follow-up study of acid-related disorders. (Trial registration number: ChiCTR2100043455.).

The role of corticotropin-releasing hormone (CRH) family in tumors.

The corticotropin-releasing hormone (CRH) family is widely distributed among the central nervous system and peripheral tissues, such as the digestive, cardiovascular, immune, reproductive, endocrine systems. The CRH family members are widely involved in the regulation of human cell biological processes, immune response, and regulation of inflammatory processes that can affect the occurrence and development of tumors. At present, CRH family members and their receptors can be detected in many tumor tissues, and some people think that members of the CRH family may be potential tumor treatment targets as they can affect cellular processes, such as proliferation, migration, invasion, and apoptosis. However currently, there is no systematic introduction to the relationship between the CRH family and various tumors. This review introduces the molecular regulation of the CRH family in tumor formation and seeks further targeted therapy.

Massive gastric bleeding - perforation of pancreatic pseudocyst into the stomach: A case report and review of literature.

BACKGROUND: Pancreatic pseudocyst may cause serious gastrointestinal complications including necrosis, infection, and perforation of the gastrointestinal tract wall, but massive gastric bleeding is very rare. CASE: We report a rare case of a 49-year-old man with life-threatening gastric bleeding from a pseudoaneurysm of the splenic artery perforating the stomach induced by pancreatic pseudocyst. During hospitalization, gastroscopy revealed a bare blood vessel in an ulcer-like depression of the greater gastric curvature, and computed tomography scan confirmed a pancreatic pseudocyst invading part of the spleen and gastric wall of the greater curvature. Arteriography showed that the bare blood vessel originated from a pseudoaneurysm of the splenic artery. The bleeding was controlled by the trans-arterial embolization, the patient's recovery was rapid and uneventful. CONCLUSION: Massive gastrointestinal bleeding could be a rare complication of pancreatic pseudo aneurysm.

Localized primary gastric amyloidosis: Three case reports.

BACKGROUND: Localized primary gastric amyloidosis is a rare disorder characterized by the extracellular deposition of insoluble fibrillary protein in the stomach and can mimic various diseases on endoscopic examination, including gastrointestinal stromal tumors, gastric cancer and ulcers. CASE SUMMARIES: Here, we report a series of three cases of localized gastric amyloidosis mimicking gastric mucosa-associated lymphoid tissue (MALT) lymphoma on endoscopic examination that were evaluated over the past ten years in our hospital. The different detection times of this rare disease resulted in three completely different outcomes, indicating the strong importance of early detection, diagnosis and treatment. The difficulties encountered in making an accurate diagnosis and differential diagnosis are highlighted, and this report provides clinical experience for the diagnosis of localized primary gastric amyloidosis. CONCLUSION: Localized gastric amyloidosis is a rare metabolic disease that resembles MALT lymphoma. Early detection, diagnosis and treatment of localized gastric amyloidosis result in an excellent prognosis.

Celecoxib attenuates hepatocyte apoptosis by inhibiting endoplasmic reticulum stress in thioacetamide-induced cirrhotic rats.

BACKGROUND: Endoplasmic reticulum (ER) stress is an important mechanism in the progression of chronic and acute liver diseases, especially in the progression and recovery of liver fibrosis. Excessive and long-term ER stress induces apoptosis. ER stress-induced apoptosis is considered to be an important pathway in the development of liver fibrosis. Cyclooxygenase-2 (COX-2) induction is also closely related to ER stress. In our previous studies, we showed that celecoxib, a COX-2 inhibitor, improves liver fibrosis and portal hypertension. However, the role and mechanism of celecoxib in alleviating liver fibrosis remain unclear. AIM: To investigate whether celecoxib alleviates liver fibrosis by inhibiting hepatocyte apoptosis via the ER stress response. METHODS: Cirrhosis was induced by intraperitoneal injections of thioacetamide (TAA) for 16 wk (injection dose is 200 mg/kg per 3 d for the first 8 wk and 100 mg /kg per 3 d after 8 wk). Thirty-six male Sprague-Dawley rats were randomly divided into three groups, namely, control group, TAA group, and TAA + celecoxib group. In the last 8 wk, TAA-induced cirrhotic rats received celecoxib (20 mg/kg/day) or the vehicle by gastric gavage. After 16 wk, the rats were sacrificed, and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin (ALB) were detected. The hepatic fibrosis areas were evaluated by Sirius red staining and the degree of fibrosis was assessed by measuring the level of hydroxyproline. ER stress levels were evaluated by detecting the marker proteins glucose-regulated protein 78 (GRP78), CCAAT/enhancer binding protein homologous protein (CHOP), PKR-like ER protein kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring enzyme 1 alpha (IRE1α). Apoptosis levels were evaluated by detecting caspase-12 and caspase-3. RESULTS: The serum ALT and AST levels in the liver were significantly reduced by celecoxib; however, the serum ALB had no significant changes. Celecoxib significantly reduced the degree of liver fibrosis and the levels of hydroxyproline (-38% and -25.7%, respectively, P < 0.01). Celecoxib ameliorated ER stress by reducing the level of GRP78 compared to the TAA group (P < 0.05). Consistently, after celecoxib administration, the upregulation of TAA-induced hepatic apoptosis markers (caspase-12 and caspase-3) and CHOP were significantly inhibited. In addition, after celecoxib treatment, the expression of key molecules associated with ER stress (PERK, ATF6, and IRE1) was decreased (P < 0.05). CONCLUSION: Therapeutic administration of celecoxib effectively reduces hepatic apoptosis in TAA-induced cirrhotic rats. The mechanism of action may be attributed to the suppression of CHOP expression, which subsequently inhibits ER stress.

Overview of organic anion transporters and organic anion transporter polypeptides and their roles in the liver.

Organic anion transporters (OATs) and organic anion transporter polypeptides (OATPs) are classified within two SLC superfamilies, namely, the SLC22A superfamily and the SLCO superfamily (formerly the SLC21A family), respectively. They are expressed in many tissues, such as the liver and kidney, and mediate the absorption and excretion of many endogenous and exogenous substances, including various drugs. Most are composed of 12 transmembrane polypeptide chains with the C-terminus and the N-terminus located in the cell cytoplasm. OATs and OATPs are abundantly expressed in the liver, where they mainly promote the uptake of various endogenous substrates such as bile acids and various exogenous drugs such as antifibrotic and anticancer drugs. However, differences in the locations of glycosylation sites, phosphorylation sites, and amino acids in the OAT and OATP structures lead to different substrates being transported to the liver, which ultimately results in their different roles in the liver. To date, few articles have addressed these aspects of OAT and OATP structures, and we study further the similarities and differences in their structures, tissue distribution, substrates, and roles in liver diseases.

Unexplained abdominal pain due to a fish bone penetrating the gastric antrum and migrating into the neck of the pancreas: A case report.

BACKGROUND: Ingestion of foreign bodies results in gastrointestinal perforation in approximately 1% of patients, and fish bones are the objects that most commonly lead to bowel perforation. When it does occur, the terminal ileum is the most common site of perforation, followed by the duodenal C-loop. However, involvement of the pancreas is very rare. Because clinical symptoms are nonspecific and gastrointestinal perforation may present as only odynophagia or abdominal pain, a definite preoperative diagnosis and clinical intervention may be delayed. CASE SUMMARY: We report the case of a 32-year-old man who presented to our hospital because of abdominal pain that had worsened over 5 d. He had no significant past history except that he had eaten fish 1 wk previously. Upper endoscopy revealed an irregular submucosal tumor on the front wall of the gastric antrum. Endoscopic ultrasonography and computed tomography showed a fish bone penetrating the gastric antrum and migratingin to the neck of the pancreas. The patient underwent laparoscopic surgery and had no complications one week after the operation. CONCLUSION: A recent history of foreign body ingestion and imaging examinations are helpful for diagnosis of unexplained abdominal pain caused by foreign bodies.

Neurofibromatosis type 1-associated multiple rectal neuroendocrine tumors: A case report and review of the literature.

Neurofibromatosis type 1 (NF-1) is commonly associated with benign or malignant tumors in both the central and peripheral nervous systems. However, rare cases of NF-1-associated multiple rectal neuroendocrine tumors have been reported. This report describes a case of a 39 year old female with NF-1 and intermittent hematochezia as a primary symptom. Physical examination showed multiple subcutaneous nodules and café au lait spots with obvious scoliosis of the back. Imaging examinations and colonoscopy found malformation of the left external iliac vein and multiple gray-yellow nodules with varying sizes and shapes in the rectal submucosal layer. Histological and immunohistochemical results suggested multiple rectal neuroendocrine tumors, a rare disease with few appreciable symptoms and a particularly poor prognosis. The patient with NF-1 presented here had not only multiple rectal neuroendocrine neoplasms but also vascular malformations, scoliosis and other multiple system lesions. This case therefore contributes to improving clinical understanding, diagnosis and treatment of related complications for patients with NF-1 who present with associated medical conditions.

[Effects of weile powder on bicarbonate transporters CFTR SLC26A3 and SLC26A6 in gastric ulcers of rats].

OBJECTIVE: To investigate the effects of Weile Powder (WLP) on bicarbonate transporters in rats with gastric ulcers, and to probe its functional mechanisms. METHODS: The 48 SD rats were randomly divided into the normal control group, the model group, the low dose WLP group (at the daily dose of 0.075 g/mL), the middle dose WLP group (at the daily dose of 0.150 g/mL), the high dose WLP group (at the daily dose of 0.030 g/mL), and the ranitidine group (at the daily dose of 0.030 g/mL), 8 in each group. The gastric ulcer rat model was prepared by the glacial acetic acid cauterization method. Rats in each medication group were administered from the 2nd day of modeling. Rats were sacrificed after 14-day successive medication. The protein was extracted from the ulcer tissue. The protein expressions of solute carrier26A3 (SLC26A3)and solute carrier26A6 (SLC26A6) were detected using Western blot. The gastric ulcer and its peripheral tissue were sectioned. The changes of cystic fibrosis transmembrane conductance regulator (CFTR) were measured by immunofluorescence. RESULTS: Compared with the model control group, the expression levels of SLC26A3 increased in the high dose WLP group and the ranitidine group with statistical difference (P < 0.05). The expression levels of SLC26A6 increased in the high and middle dose WLP groups and the ranitidine group with statistical difference (P < 0.05). The expression level of CFTR also obviously increased in the high and middle dose WLP groups (P < 0.01). CONCLUSION: WLP could elevate the expression levels of SLC26A6, SLC26A3, and CFTR, increase the secretion of bicarbonate, thus protecting the gastric mucosa.

Duodenal acidity "sensing" but not epithelial HCO3- supply is critically dependent on carbonic anhydrase II expression.

Carbonic anhydrase (CA) is strongly expressed in the duodenum and has been implicated in a variety of physiological functions including enterocyte HCO(3)(-) supply for secretion and the "sensing" of luminal acid and CO(2). Here, we report the physiological role of the intracellular CAII isoform involvement in acid-, PGE(2,) and forskolin-induced murine duodenal bicarbonate secretion (DBS) in vivo. CAII-deficient and WT littermates were studied in vivo during isoflurane anesthesia. An approximate 10-mm segment of the proximal duodenum with intact blood supply was perfused under different experimental conditions and DBS was titrated by pH immediately. Two-photon confocal microscopy using the pH-sensitive dye SNARF-1F was used to assess duodenocyte pH(i) in vivo. After correction of systemic acidosis by infusion of isotonic Na(2)CO(3), basal DBS was not significantly different in CAII-deficient mice and WT littermates. The duodenal bicarbonate secretory response to acid was almost abolished in CAII-deficient mice, but normal to forskolin- or 16,16-dimethyl PGE(2) stimulation. The complete inhibition of tissue CAs by luminal methazolamide and i.v. acetazolamide completely blocked the response to acid, but did not significantly alter the response to forskolin. While duodenocytes acidified upon luminal perfusion with acid, no significant pH(i) change occurred in CAII-deficient duodenum in vivo. The results suggest that CA II is important for duodenocyte acidification by low luminal pH and for eliciting the acid-mediated HCO(3)(-) secretory response, but is not important in the generation of the secreted HCO(3)(-) ions.

Prevalence of peptic ulcer in dyspeptic patients and the influence of age, sex, and Helicobacter pylori infection.

We investigated the prevalence of peptic ulcer in dyspeptic patients in China to analyze the influence of age, sex, and Helicobacter pylori (H. pylori) infection. The results showed that the prevalence of gastric and duodenal ulcer increased with age. In patients under 60 years old, the prevalence of duodenal and gastric ulcers in females was markedly lower than that in males, especially the prevalence of duodenal ulcer. The prevalence of duodenal ulcer and gastric ulcer in H. pylori-infected patients was markedly higher than in patients without H. pylori infection. In the patients under 60 years old, sex differences were still seen in both H. pylori-positive and H. pylori-negative patients. The prevalence of gastric and duodenal ulcers was markedly increased with age in both H. pylori-positive and H. pylori-negative patients. Multivariate logistic regression analysis showed that age, male sex, and H. pylori infection were three independent risk factors for gastric and duodenal ulcers.

Phosphatidylinositol 3-kinase is involved in prostaglandin E2-mediated murine duodenal bicarbonate secretion.

Prostaglandin E(2) (PGE(2)) plays an important role in the regulation of duodenal bicarbonate (HCO(3)(-)) secretion, but its signaling pathway(s) are not fully understood. In the present study, we investigated the signaling pathways involved in PGE(2)-mediated duodenal HCO(3)(-) secretion. Murine duodenal mucosal HCO(3)(-) secretion was examined in vitro in Ussing chambers by pH-stat titration in the presence of a variety of signal transduction modulators. Phosphatidylinositol 3-kinase (PI3K) activity was measured by immunoprecipitation of PI3K and ELISA, and Akt phosphorylation was measured by Western analysis with anti-phospho-Akt and anti-Akt antibodies. PGE(2)-stimulated duodenal HCO(3)(-) secretion was reduced by the cAMP-dependent signaling pathway inhibitors MDL-12330A and KT-5720 by 23% and 20%, respectively; the Ca(2+)-influx inhibitor verapamil by 26%; and the calmodulin antagonist W-13 by 24%; whereas the PI3K inhibitors wortmannin and LY-294002 reduced PGE(2)-stimulated HCO(3)(-) secretion by 51% and 47%, respectively. Neither the MAPK inhibitor PD-98059 nor the tyrosine kinase inhibitor genistein altered PGE(2)-stimulated HCO(3)(-) secretion. PGE(2) application caused a rapid and concentration-dependent increase in duodenal mucosal PI3K activity and Akt phosphorylation. These results demonstrated that PGE(2) activates PI3K in duodenal mucosa and stimulates duodenal HCO(3)(-) secretion via cAMP-, Ca(2+)-, and PI3K-dependent signaling pathways.

Protein kinase C potentiates cAMP-stimulated mouse duodenal mucosal bicarbonate secretion in vitro.

PKC has been shown to regulate epithelial Cl(-) secretion in a variety of models. However, the role of PKC in duodenal mucosal bicarbonate secretion is less clear. We aimed to investigate the role of PKC in regulation of duodenal mucosal bicarbonate secretion. Bicarbonate secretion by murine duodenal mucosa was examined in vitro in Ussing chambers using a pH-stat technique. PKC isoform expression and activity were assessed by Western blotting and in vitro kinase assays, respectively. PMA (an activator of PKC) alone had no effect on duodenal bicarbonate secretion or short-circuit current (I(sc)). When PMA and dibutyryl-cAMP (db-cAMP) were added simultaneously, PMA failed to alter db-cAMP-stimulated duodenal bicarbonate secretion or I(sc) (P > 0.05). However, a 1-h preincubation with PMA potentiated db-cAMP-stimulated duodenal bicarbonate secretion and I(sc) in a concentration-dependent manner (from 10(-8) to 10(-5)M) (P < 0.05). PMA preincubation had no effects on carbachol- or heat-stable toxin-stimulated bicarbonate secretion. Western blot analysis revealed that PKCalpha, -gamma, -epsilon, -, -micro, and -iota/lambda were expressed in murine duodenal mucosa. Ro 31-8220 (an inhibitor active against PKCepsilon, -alpha, -beta, and -gamma), but not Gö 6983 (an inhibitor active against PKCalpha, -gamma, -beta, and -delta), reversed the potentiating effect of PMA on db-cAMP-stimulated bicarbonate secretion. PMA also time- and concentration-dependently increased the activity of PKCepsilon, an effect that was prevented by Ro 31-8220 but not Gö 6983. These results demonstrate that activation of PKC potentiates cAMP-stimulated duodenal bicarbonate secretion, whereas it does not modify basal secretion. The effect of PKC on cAMP-stimulated bicarbonate secretion is mediated by the PKCepsilon isoform.

A role for CagA/VacA in Helicobacter pylori inhibition of murine duodenal mucosal bicarbonate secretion.

Duodenal mucosal bicarbonate secretion is diminished in patients with Helicobacter pylori (HP)-associated duodenal ulcer disease. We examined whether HP water extracts inhibit murine duodenal mucosal bicarbonate secretion in vitro, and the mechanisms involved. Murine duodenal mucosae were mounted in Ussing chambers. Short-circuit current and bicarbonate secretion was measured. CagA/VacA-positive HP water extract (HPWE+/+) markedly inhibited PGE2-, carbachol-, or the calcium ionophore A23187-stimulated bicarbonate secretion in a dose-dependent manner. While 3-isobutyl-1-methylxanthine-stimulated bicarbonate secretion was not affected by HPWE+/+, HPWE+/+ did diminish forskolin-stimulated bicarbonate secretion. HPWE+/+ markedly diminished PGE2-induced increases in duodenal mucosal cAMP. CagA/VacA of HP decreases Ca2+-mediated bicarbonate secretion downstream of increases in intracellular Ca2+. Dimunition of PGE2-stimulated bicarbonate secretion occurs, in part, by inhibition of adenylate cyclase, which leads to decreased cAMP levels. The ability of virulent HP strains to inhibit duodenal bicarbonate secretion through multiple intracellular pathways likely contributes to the pathogenesis of HP-associated duodenal ulcer disease.

5-HT induces duodenal mucosal bicarbonate secretion via cAMP- and Ca2+-dependent signaling pathways and 5-HT4 receptors in mice.

In previous studies, we have found that 5-hydroxytryptamine (5-HT) is a potent stimulant of duodenal mucosal bicarbonate secretion (DMBS) in mice. The aim of the present study was to determine the intracellular signaling pathways and 5-HT receptor subtypes involved in 5-HT-induced DMBS. Bicarbonate secretion by murine duodenal mucosa was examined in vitro in Ussing chambers. 5-HT receptor involvement in DMBS was inferred from pharmacological studies by using selective 5-HT receptor antagonists and agonists. The expression of 5-HT(4) receptor mRNA in duodenal mucosa and epithelial cells was analyzed by RT-PCR. cAMP-dependent signaling pathway inhibitors MDL-12330A, Rp-cAMP, and H-89 and Ca(2+)-dependent signaling pathway inhibitors verapamil and W-13 markedly reduced 5-HT-stimulated duodenal bicarbonate secretion and short-circuit current (I(sc)), whereas cGMP-dependent signaling pathway inhibitors NS-2028 and KT-5823 failed to alter these responses. Both SB-204070 and high-dose ICS-205930 (selective 5-HT(4) receptor antagonists) markedly inhibited 5-HT-stimulated bicarbonate secretion and I(sc), whereas methiothepine (5-HT(1) receptor antagonist), ketanserin (5-HT(2) receptor antagonist), and a low concentration of ICS-205930 (5-HT(3) receptor antagonist) had no effect. RS-67506 (partial 5-HT(4) receptor agonist) concentration-dependently increased bicarbonate secretion and I(sc), whereas 5-carboxamidotryptamine (5-HT(1) receptor agonist), alpha-methyl-5-HT (5-HT(2) receptor agonist), and phenylbiguanide (5-HT(3) receptor agonist) did not significantly increase bicarbonate secretion or I(sc). RT-PCR analysis confirmed the expression of 5-HT(4) receptor mRNA in murine duodenal mucosa and epithelial cells. These results demonstrate that 5-HT regulates DMBS via both cAMP- and Ca(2+)-dependent signaling pathways and 5-HT(4) receptors located in the duodenal mucosa and/or epithelial cells.

Effect of 5-hydroxytryptamine on duodenal mucosal bicarbonate secretion in mice.

BACKGROUND & AIMS: 5-hydroxytryptamine (5-HT) is an important neurotransmitter and intercellular messenger that modulates many gastrointestinal functions. Because little is known about the role of 5-HT in the regulation of duodenal bicarbonate secretion, we examined the role of 5-HT on duodenal bicarbonate secretion and define neural pathways involved in the actions of 5-HT. METHODS: Duodenal mucosa from National Institutes of Health Swiss mice was stripped of seromuscular layers and mounted in Ussing chambers. The effect of 5-HT on duodenal bicarbonate secretion was determined by the pH stat technique. Acetylcholine (ACh) release from duodenal mucosa was assessed by preincubating the tissue with [(3)H] choline and measuring 5-HT-evoked release of tritium. RESULTS: 5-HT added to the serosal bath markedly stimulated duodenal bicarbonate secretion and short circuit current (Isc) in a dose-dependent manner (10(-7) mol/L to 10(-3) mol/L; P < 0.0001), whereas mucosally added 5-HT was without effect. 5-HT-stimulated bicarbonate secretion was independent of luminal Cl(-). Pretreatment with tetrodotoxin (TTX) (10(-6) mol/L) or atropine (10(-5) mol/L) markedly reduced 5-HT-stimulated duodenal bicarbonate secretion (by 60% and 65%, respectively; P < 0.001) and Isc (by 45% and 27%, respectively; P < 0.001 and P < 0.05). Pretreatment with N(omega)-nitro-l-arginine methyl ester (l-NAME) (10(-3) mol/L), propranolol (10(-5) mol/L), or phentolamine (10(-5) mol/L) did not significantly alter 5-HT-stimulated duodenal mucosal bicarbonate secretion or Isc. 5-HT concentration-dependently evoked ACh release from duodenal mucosal preparations (P < 0.0001). TTX markedly inhibited 5-HT-evoked ACh release (P < 0.001). CONCLUSIONS: 5-HT is a potent activator of duodenal mucosal bicarbonate secretion in mice. Duodenal bicarbonate secretion induced by 5-HT in vitro occurs principally via a cholinergic neural pathway.