Isosmotic modulation of Ca2+-regulated exocytosis in guinea-pig antral mucous cells: role of cell volume. (1/848)

1. Exocytotic events and changes of cell volume in mucous cells from guinea-pig antrum were examined by video-enhanced optical microscopy. 2. Acetylcholine (ACh) evoked exocytotic events following cell shrinkage, the frequency and extent of which depended on the ACh concentration. ACh actions were mimicked by ionomycin and thapsigargin, and inhibited by Ca2+-free solution and Ca2+ channel blockers (Ni2+, Cd2+ and nifedipine). Application of 100 microM W-7, a calmodulin inhibitor, also inhibited the ACh-induced exocytotic events. These results indicate that ACh actions are mediated by intracellular Ca2+ concentration ([Ca2+]i) in antral mucous cells. 3. The effects of ion channel blockers on exocytotic events and cell shrinkage evoked by ACh were examined. Inhibition of KCl release (quinine, Ba2+, NPPB or KCl solution) suppressed both the exocytotic events and cell shrinkage evoked by ACh. 4. Bumetanide (inhibition of NaCl entry) or Cl--free solution (increasing Cl- release and inhibition of NaCl entry) evoked exocytotic events following cell shrinkage in unstimulated antral mucous cells and caused further cell shrinkage and increases in the frequency of exocytotic events in ACh-stimulated cells. However, Cl--free solution did not evoke exocytotic events in unstimulated cells in the absence of extracellular Ca2+, although cell shrinkage occurred. 5. To examine the effects of cell volume on ACh-evoked exocytosis, the cell volume was altered by increasing the extracellular K+ concentration. The results showed that cell shrinkage increases the frequency of ACh-evoked exocytotic events and cell swelling decreases them. 6. Osmotic shrinkage or swelling caused the frequency of ACh-evoked exocytotic events to increase. This suggests that the effects of cell volume on ACh-evoked exocytosis under anisosmotic conditions may not be the same as those under isosmotic conditions. 7. In antral mucous cells, Ca2+-regulated exocytosis is modulated by cell shrinkage under isosmotic conditions.  (+info)

Effects of duodenal distension on antropyloroduodenal pressures and perception are modified by hyperglycemia. (2/848)

Marked hyperglycemia (blood glucose approximately 15 mmol/l) affects gastrointestinal motor function and modulates the perception of gastrointestinal sensations. The aims of this study were to evaluate the effects of mild hyperglycemia on the perception of, and motor responses to, duodenal distension. Paired studies were done in nine healthy volunteers, during euglycemia ( approximately 4 mmol/l) and mild hyperglycemia ( approximately 10 mmol/l), in randomized order, using a crossover design. Antropyloroduodenal pressures were recorded with a manometric, sleeve-side hole assembly, and proximal duodenal distensions were performed with a flaccid bag. Intrabag volumes were increased at 4-ml increments from 12 to 48 ml, each distension lasting for 2.5 min and separated by 10 min. Perception of the distensions and sensations of fullness, nausea, and hunger were evaluated. Perceptions of distension (P < 0.001) and fullness (P < 0.05) were greater and hunger less (P < 0.001) during hyperglycemia compared with euglycemia. Proximal duodenal distension stimulated pyloric tone (P < 0.01), isolated pyloric pressure waves (P < 0.01), and duodenal pressure waves (P < 0.01). Compared with euglycemia, hyperglycemia was associated with increases in pyloric tone (P < 0.001), the frequency (P < 0.05) and amplitude (P < 0.01) of isolated pyloric pressure waves, and the frequency of duodenal pressure waves (P < 0.001) in response to duodenal distension. Duodenal compliance was less (P < 0.05) during hyperglycemia compared with euglycemia, but this did not account for the effects of hyperglycemia on perception. We conclude that both the perception of, and stimulation of pyloric and duodenal pressures by, duodenal distension are increased by mild hyperglycemia. These observations are consistent with the concept that the blood glucose concentration plays a role in the regulation of gastrointestinal motility and sensation.  (+info)

Role of apoptosis induced by Helicobacter pylori infection in the development of duodenal ulcer. (3/848)

BACKGROUND: Helicobacter pylori affects gastric epithelium integrity by acceleration of apoptosis. However, it remains unclear what product of the bacteria causes apoptosis, or whether or not the apoptosis is involved in the development of ulcers. AIMS: To elucidate the factor from H pylori that causes acceleration of apoptosis and the role of apoptosis in the development of duodenal ulcer in H pylori infection. PATIENTS: Five H pylori negative healthy volunteers, 47 H pylori positive patients with duodenal ulcer, and 35 H pylori positive patients with gastric ulcer. METHODS: An endoscopic examination was carried out to diagnose ulcers and determine their clinical stage. To analyse apoptosis, a cell cycle analysis was performed using biopsy specimens. RESULTS: There was a significant correlation between the urease activity of the H pylori strain and the level of apoptosis induced by this bacterial strain. Moreover, in duodenal ulcer patients infected with H pylori, the patients with an active ulcer exhibited a significantly higher level of apoptosis than those with ulcers at both the healing and scarring stages. CONCLUSION: These findings suggest that acceleration of apoptosis in the antral mucosa caused by the urease of H pylori plays a crucial role in the development of ulcers in the duodenum.  (+info)

Regional and functional differences of 5-hydroxytryptamine-receptor subtypes in guinea pig stomach. (4/848)

Functions and the presence of 5-hydroxytryptamine (5-HT) receptors in the fundus, corpus and antrum of the guinea pig stomach were examined by measuring contractile force and acetylcholine (ACh) release. Stimulation of the 5-HT1 receptor caused tetrodotoxin (TTX)-insensitive relaxations in the preparations from 3 regions. Stimulation of the 5-HT2 receptor caused TTX-insensitive contractions in the preparations of fundus and antrum. Stimulation of 5-HT3 receptors caused contractions that were sensitive to TTX and atropine and enhanced the outflow of [3H]ACh from preparations of only antrum. Stimulation of 5-HT4 receptors caused contractions of antral strips and decreased relaxations of corporal strips and enhanced the outflow of [3H]ACh from the preparations of both corpus and antrum. In the guinea pig stomach, the fundus possesses relaxant 5-HT1 receptor < contractile 5-HT2 receptors and caused the contractile response to 5-HT. The corpus possesses relaxant 5-HT1 receptors and relaxant receptors other than 5-HT1, 5-HT2, 5-HT3 and 5-HT4 receptors > contractile 5-HT4 receptor, and therefore 5-HT caused relaxations. The antrum possesses relaxant 5-HT1 receptor < contractile 5-HT2, 5-HT3 and 5-HT4 receptors, and thus 5-HT caused contractions.  (+info)

Indomethacin-induced gastric antral damage in hamsters: are neutrophils involved? (5/848)

BACKGROUND: A direct role for neutrophils in the pathophysiology of indomethacin-induced gastric damage is controversial. Therefore, such damage was evaluated in hamsters. METHODS: Gastric antral damage was evaluated 4 h after the oro-gastric administration of indomethacin (30 mg/kg). Prior to indomethacin, hamsters were treated with various pharmacological agents: rebamipide, methotrexate or anti-neutrophil serum (ANS). The number of circulating neutrophils was determined from Wright-Giemsa stained blood smears. Myeloperoxidase (MPO) activity was measured as a marker of gastric antral neutrophil infiltration. RESULTS: Indomethacin caused primarily gastric antral damage. By histology, this damage did not penetrate the muscularis mucosa. A significant increase in gastric antral MPO activity was also found in indomethacin-treated hamsters. Rebamipide decreased macroscopic gastric antral damage in a dose-related fashion. Methotrexate treatment reduced the circulating blood neutrophil number by 38-44%, but did not affect gastric damage. ANS treatment resulted in near complete neutropenia, and also in a substantial reduction (84%) in gastric antral MPO activity. However, gastric antral damage was not significantly altered by ANS. CONCLUSIONS: Neutrophils are not directly involved in the pathophysiology of indomethacin-induced damage to the hamster gastric antrum.  (+info)

Proximal gastric vagotomy: effects of two operative techniques on clinical and gastric secretory results. (6/848)

PGV performed in 39 patients by separating the lesser omentum from the stomach beginning 6 or 7 cm proximal to the pylorus and skeletonizing the distal 1 to 2 cm of esophagus was followed by 15.4% of proven and 10.2 of suspected recurrent ulcers. Insulin tests were done during the first 3 months postoperatively on 31 of the patients, including the 6 with proven and the 4 with suspected recurrent ulcers. The peak acid output to insulin minus tha basal acid output (PAOI-BAO) was less than 5 mEq/hr in 16 cases (52%) and from 5 to 25 mEq/hr in the remaining 15 cases. In 6 patients with proven recurrent ulcer, PAOI-BAO averaged 21.9 mEq/hr (range, 11.3 to 41.8); in the 4 patients with suspected recurrence, 9.5 (range, 4.4 to 11.8). The operative technique was changed in one respect; the distal 5 to 7.5 cm of the esophagus was skeletonized. In 14 patients, the mean PAOI-BAO +/- S.E. within 3 months of PGV was 1985 +/- 0.7 mEq/hr, and 13 of 14 values were less than 5 mEq/hr. One patient developed recurrent ulcer and required re-operation; this patient's value for PAO-BAO was 1.8 mEq/hr. The results show quantitatively that great differences in the completeness of PGV result from differences in the periesophageal dissection and emphasize its importance if optimal results are to be obtained and, especially, if the efficacy of the operation is to be judged.  (+info)

Downregulation of Galphaq-11 protein expression in guinea pig antral and colonic circular muscle during pregnancy. (7/848)

Pregnancy has an inhibitory effect on motility of the gastrointestinal tract. The present study was designed to examine the mechanisms responsible for antral and colonic hypomotility in pregnant guinea pigs. Circular smooth muscle cells from the antrum and left colon were isolated by enzymatic digestion with collagenase from pregnant and nonpregnant guinea pigs. Contractile responses to agonists were expressed as percent shortening from resting cell length. The function of G proteins in antral and colonic circular smooth muscle was assessed by [35S]guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) binding induced by CCK-8 and G protein quantitation. The contraction of antral and colonic circular smooth muscle from pregnant guinea pigs was reduced in response to CCK-8 and to GTPgammaS but was normal in response to KCl and D-myo-inositol 1,4,5-trisphosphate compared with nonpregnant animals. The stimulation of [35S]GTPgammaS binding to Galphaq-11 induced by 1 microM CCK-8 was significantly lower in antral and colonic circular smooth muscle from pregnant guinea pigs than that in controls. Furthermore, Western blot analysis showed a decreased Galphaq-11 and an increased Gsalpha protein content in both tissues during pregnancy. It is concluded that pregnancy appears to impair gastrointestinal circular smooth muscle contractility by downregulating G proteins such as Galphaq-11 protein, which mediates muscle contraction, and upregulating Gsalpha protein, which mediates muscle relaxation.  (+info)

Gastric antral vascular ectasia in cirrhotic patients: absence of relation with portal hypertension. (8/848)

BACKGROUND: Portal hypertensive gastropathy and gastric antral vascular ectasia (GAVE) are increasingly recognised as separate entities. The pathogenic role of portal hypertension for the development of GAVE is still controversial. AIMS: To evaluate the effects of portal decompression on chronic bleeding related to GAVE in cirrhotic patients. METHODS: Eight patients with cirrhosis and chronic blood loss related to GAVE were included. GAVE was defined endoscopically and histologically. RESULTS: All patients had severe portal hypertension (mean portocaval gradient (PCG) 26 mm Hg) and chronic low grade bleeding. Seven patients underwent transjugular intrahepatic portosystemic shunt (TIPS) and one had an end to side portacaval shunt. Rebleeding occurred in seven patients. In these, TIPS was found to be occluded after 15 days in one patient; in the other six, the shunt was patent and the PCG was below 12 mm Hg in five. In the responder, PCG was 16 mm Hg. Antrectomy was performed in four non-responders; surgery was uneventful, and they did not rebleed after surgery, but two died 11 and 30 days postoperatively from multiorgan failure. In one patient, TIPS did not control GAVE related bleeding despite a notable decrease in PCG. This patient underwent liver transplantation 14 months after TIPS; two months after transplantation, bleeding had stopped and the endoscopic appearance of the antrum had normalised. CONCLUSIONS: Results suggest that GAVE is not directly related to portal hypertension, but is influenced by the presence of liver dysfunction. Antrectomy is a therapeutic option when chronic bleeding becomes a significant problem but carries a risk of postoperative mortality.  (+info)