Plasma Somatostatin-like immunoreactivity in chemically sympathectomized dogs

The present study was designed to determine the role of the adrenergic nerves upon basal and postprandial gastric and pancreatic SLI release. In 19 chemically sympathectomized dogs peripheral venous plasma SLI levels in the basal and postprandial state were significantly below those of 30 controls for the first 135 min after the ingestion of a fat-protein meal. To determine the origin of this reduction, the SLI release from fundus, antrum and pancreas was studied in anesthetized dogs during the gastric phase of a meal at either pH 7 or pH 2. In response to a liver meal at pH 7 fundic, antral and pancreatic vein SLI levels were below the control and the rise in inferior vena cava SLI was abolished. In response to a liver meat at pH 2, the rise in antral and pancreatic vein SLI as clearly reduced in the sympathectomized dogs, while the decrease in fundic SLI was not influenced. The data demonstrate that adrenergic innervation plays a role in basal and postprandial SLI release from the stomach and pancreas.     

Antilysozyme activity and antibiotic resistance of periulcerous zone microflora in patients with gastric and duodenal ulcer

Antilysozyme activity (ALA) as well as antibiotic resistance were detected in 133 microbial cultures isolated from bioptic specimens of the mucous membrane of the ulcerous and periulcerous zones, taken from patients with gastric and duodenal ulcer. In 85.7-94.7% of cases Gram positive cocci and in 62.5% of cases Gram-positive bacilli showed no ALA. 50% of Gram negative bacteria cultures lacked ALA, while the remaining 50% exhibited this activity, on the average, 2.36 +/- 1.40 mkg/ml. Lysozyme activity was determined in 33.3% of the isolated staphylococci strains both with and without ALA. Staphylococci isolated from the gastric mucosa of healthy controls had no ALA in 33.3% of cases, and in 66.7% of cases ALA was equal to 2 mkg/ml. Gram positive coccal microflora showed, mainly, high sensitivity to antibiotics. In Gram negative bacteria antibiotic resistance was determined in 44.3 +/- 21.2% of the isolates. In Gram negative microorganisms correlation between ALA and antibiotic resistance was observed. From the periulcerous zone of patients with gastric and duodenal ulcer persistence associated Gram negative microorganisms were mainly isolated.     

Effect of vasoactive intestinal peptide, peptide histidine isoleucine and growth hormone-releasing factor-40 on bombesin-like immunoreactivity, somatostatin and gastrin release from the perfused rat stomach

Bombesin-like immunoreactivity (BLI) has been demonstrated in neurons of the gastrointestinal tract and gastric BLI secretion can be demonstrated in response to the classical neurotransmitter acetylcholine. Since structurally related peptides VIP, PHI and GRF have to be considered as peptidergic neurotransmitters it was of interest to determine their effect on gastric BLI secretion. Additionally, somatostatin (SLI) and gastrin secretion was examined. The isolated stomach of overnight fasted rats was perfused with Krebs-Ringer buffer via the celiac artery and the effluent was collected via the portal vein. The gastric lumen was perfused with isotonic saline at pH7 or pH2. All four peptides were tested at a dose of 10(-11) M and 10(-8) M at both pH levels and in addition the effect of VIP and PHI was examined at 10(-14) M and 10(-12) M during luminal pH2. At luminal pH7 VIP and PHI stimulated SLI release at 10(-8) M but had no effect on BLI or gastrin secretion. rGRF and hpGRF were both ineffective on SLI and gastrin release while rGRF inhibited and hpGRF stimulated BLI secretion. This effect was not dose related. At luminal pH2 all four peptides stimulated BLI secretion. Stimulation by PHI was already observed at a dose of 10(-14) M while VIP elicited a stimulatory effect at 10(-12) M. PHI at the two lowest concentrations of 10(-14) and 10(-12) M elicited a stimulation of SLI and gastrin release while the same doses of VIP and the higher doses of all four peptides had no effect on SLI and gastrin secretion at an acidic intraluminal pH.(ABSTRACT TRUNCATED AT 250 WORDS)     

Implication of gastrin in cyclooxygenase-2 expression in Helicobacter pylori infected gastric ulceration

Gastroduodenal ulcerations have worldwide distribution and the infection with Helicobacter pylori (HP) has been implicated in pathogenesis of this disease. The HP infection is usually accompanied by hypergastrinemia and enhanced generation of prostaglandins (PG), both implicated in the pathogenesis of peptic ulcerations but no study has been undertaken to assess the relationship between the HP infection and coexpression of gastrin and cyclooxygenases (COX), the rate limiting enzymes in the PG production. Since HP infection, usually accompanying peptic ulcerations, results in increased release of gastrin, a potent gastric mitogen that might be capable to induce COX-2 and to generate PG, we decided 1) to compare the seroprevalence of HP and its cytotoxic protein, CagA, in gastric ulcer patients with those in age- and gender-matched controls; 2) to determine the gene expression of gastrin and its receptors (CCK(B)-R) at the margin of gastric ulcer and in the mucosa of antrum and corpus before and after successful eradication of HP, 3) to assess the plasma levels and gastric luminal contents of gastrin before and after HP eradication and 4) to examine the mRNA and enzyme protein expression of COX-1 and COX-2 as well as the PGE2 generation in ulcer margin tissue and gastric antral and fundic mucosa before and after the HP eradication. The trial material included 20 patients with gastric ulcer and 40 age- and gender-matched controls. Anti-HP and anti-CagA IgG seroprevalence was estimated by specific antisera using ELISA tests. Gene expressions of gastrin, CCK(B)-R, COX-1 and COX-2 were examined using RT-PCR with beta-actin as a reference and employing Western blotting for COX-2 expression, while gastrin and PGE2 were measured by RIA. All gastric ulcers were located at smaller curvature within the antral mucosal area. The seroprevalence of HP, especially that expressing CagA, was significantly higher in gastric ulcers (85%) than in controls (62.5%). Both gastrin and CCK(B)-R mRNA were detected by RT-PCR in ulcer margin and gastrin mRNA was overexpressed in remaining antral mucosa, while CCK(B)-R mRNA was overexpressed in fundic mucosa of HP infected patients. Similarly, COX-2 mRNA and protein were found in margin of gastric ulcer and in the HP infected antral and fundic mucosa but not in the mucosa of HP eradicated patients in whom ulcers completely healed and gastrin was expressed only in antrum, CCK(B)-R only in corpus, while COX-1 was detected both in antrum and corpus. HP positive gastric ulcer patients showed about three times higher levels of plasma immunoreactive gastrin and about 50% higher luminal gastrin contents than the HP negative controls and this increased plasma and luminal gastrin was normalized following the HP eradication. A significant fall in gastrin and CCK(B)-R mRNA expression was noticed six weeks after HP eradication in gastric antral and fundic mucosa, while COX-2 mRNA completely disappeared after this treatment. We conclude that 1) HP infected gastric ulcer margin coexpresses gastrin, its receptors (CCK(B)-R), and COX-2; 2) HP infection may be implicated in gastric ulceration via increased release of gastrin that could be responsible for the overexpression of COX-2 that in turn could help ulcer healing through the stimulation of mucosal cell growth, restoration of the glandular structure and angiogenesis in the ulcer area and 3) gastrin produced in HP infected antral mucosa seems to be involved in the induction of COX-2 and PG production by this enzyme and this may contribute to the ulcer healing.     

Effect of indomethacin on bombesin-like immunoreactivity, somatostatin and gastrin secretion from rat stomach

In the present study the effect of indomethacin-induced prostaglandin deficiency was examined on the release of bombesin-like immunoreactivity (BLI), a putative peptidergic neurotransmitter, from the isolated perfused rat stomach. In addition, gastrin and somatostatin (SLI) secretion was determined. Pretreatment of rats with indomethacin (2 mg/kg X h) resulted in a 3-fold increase of basal BLI secretion. In response to acetylcholine (2 X 10(-6) M) BLI rose from 2,000 to 4,000 pg/min, whereas in controls BLI increased from 400 to 1,400 pg/min. While absolute values for BLI secretion were higher in indomethacin-treated stomachs the relative increase above baseline was lower (100 vs. 250%). In control rats the increase in BLI secretion in response to acetylcholine was abolished when the acidity in the gastric lumen was increased from pH 7 to pH 2. After indomethacin, however, the stimulatory effect of acetylcholine during luminal pH 7 and pH 2 was identical. The decrease of SLI by acetylcholine at luminal pH 7 was abolished in indomethacin-treated stomachs in response to 10(-6) M acetylcholine, and 2 X 10(-6) M had even a stimulatory effect on SLI secretion. Indomethacin pretreatment reduced gastrin secretion at luminal pH 7. These data demonstrate that endogenous prostaglandins exert an inhibitory tone on basal and stimulated BLI and stimulated SLI secretion in the rat stomach. It is suggested that endogenous prostaglandins also inhibit the release of a peptidergic neurotransmitter, similar to their effect on the classical neurotransmitters acetylcholine and norepinephrine.     

Mechanisms of proton-induced stimulation of CGRP release from rat antrum

Mechanisms of acid-evoked CGRP release from gastric afferent nerves were investigated in rat antral mucosal/submucosal tissues. Low pH (pH 4.0, 5.0 and 6.0) stimulated antral CGRP release significantly and dose-dependently from rat antral fragments. Removal of extracellular calcium from the incubation medium resulted in significant inhibition (59%, P < 0.001) of acid (pH 4.0)-stimulated CGRP release. Conotoxin (1 x 10(-7) M), the selective blocker of N-type calcium channels, also significantly inhibited proton (pH 4.0)-induced CGRP release to values that were 74% below net stimulated levels. Neither nifedipine (1 x 10(-6) M), the L-type Ca(2+)-channel antagonist, nor indomethacin (1 x 10(-5) M), inhibitor of prostaglandin synthesis, altered acid-induced CGRP release. In contrast, ruthenium red (1 x 10(-5) M), capsaicin antagonist, almost completely prevented acid (pH 4.0)-stimulated CGRP release. Capsazepine (1 x 10(-4) M), a specific capsaicin receptor antagonist, also completely abolished acid-induced CGRP release. In conclusion, the results of these studies indicate that hydrogen ions are capable of evoking CGRP release from peripheral sensory neurons in rat antral mucosal/submucosal tissues. Proton-evoked CGRP release requires extracellular calcium and involves N-type calcium channels. Furthermore, acid appears to exert a capsaicin-like effect to evoke sensory neuropeptide release that is sensitive to capsazepine and ruthenium red. These data suggest that proton-induced antral CGRP release represents a direct action of hydrogen ions on mucosal/submucosal sensory dendritic nerve endings to effect local release of neuropeptide.     

The isolation and properties of a non-pepsin proteinase from human gastric mucosa.

1. A non-pepsin proteinase, proteinase 2, was successfully isolated free from pepsinogen (by repetitive chromatography on DEAE- and CM-celluloses) from the gastric mucosa of a patient with a duodenal ulcer and the uninvaded mucosa of a patient with a gastric adenocarcinoma. 2. Proteinases 1a and 1b, found in gastric adenocarcinoma, were not found in the gastic mucosa of these patients. 3. Proteinase 2 was shown to have an asymmetrical broad pH-activity curve with a maximum over the pH range 3.0-3.7. 4. Proteolytic activity of proteinase 2 was inhibited by pepstatin; the concentration of pepstatin giving 50% inhibition is of the order of 3nm. 5. Inhibition of proteolytic activity by carbenoxolone and related triterpenoids indicated that at pH 4.0 proteinase 2 possesses structural characteristics relating it to the pepsins and at pH 7.4 to the pepsinogens. 6. The sites of cleavage of the B-chain of oxidized insulin for proteinase 2 at pH 1.7 and pH 3.5 were shown to be similar to those previously established for human pepsin 3 and for the cathepsin E of rabbit bone marrow. 7. The non-pepsin proteinase 2 (cathepsin) of human gastric mucosa has properties more similar to cathepsin E than to the cathepsins D.     

A novel small molecule CFTR inhibitor attenuates HCO3- secretion and duodenal ulcer formation in rats

The cystic fibrosis (CF) transmembrane conductance regulator (CFTR) plays a crucial role in mediating duodenal bicarbonate (HCO(3)(-)) secretion (DBS). Although impaired DBS is observed in CF mutant mice and in CF patients, which would predict increased ulcer susceptibility, duodenal injury is rarely observed in CF patients and is reduced in CF mutant mice. To explain this apparent paradox, we hypothesized that CFTR dysfunction increases cellular [HCO(3)(-)] and buffering power. To further test this hypothesis, we examined the effect of a novel, potent, and highly selective CFTR inhibitor, CFTR(inh)-172, on DBS and duodenal ulceration in rats. DBS was measured in situ using a standard loop perfusion model with a pH stat under isoflurane anesthesia. Duodenal ulcers were induced in rats by cysteamine with or without CFTR(inh)-172 pretreatment 1 h before cysteamine. Superfusion of CFTR(inh)-172 (0.1-10 microM) over the duodenal mucosa had no effect on basal DBS but at 10 microM inhibited acid-induced DBS, suggesting that its effect was limited to CFTR activation. Acid-induced DBS was abolished at 1 and 3 h and was reduced 24 h after treatment with CFTR(inh)-172, although basal DBS was increased at 24 h. CFTR(inh)-172 treatment had no effect on gastric acid or HCO(3)(-) secretion. Duodenal ulcers were observed 24 h after cysteamine treatment but were reduced in CFTR(inh)-172-pretreated rats. CFTR(inh)-172 acutely produces CFTR dysfunction in rodents for up to 24 h. CFTR inhibition reduces acid-induced DBS but also prevents duodenal ulcer formation, supporting our hypothesis that intracellular HCO(3)(-) may be an important protective mechanism for duodenal epithelial cells.     

Effects of solution of low pH and taurocholate on release of beta-endorphin-like immunoreactivity from human duodenal mucosa in vitro

The presence of beta-endorphin-like immunoreactivity (beta-EpLI) in human duodenum and its release were studied. beta-EpLI was detected in the duodenum (mucosa, 26.7 +/- 6.3 pmol/g wet weight, mean +/- SEM; remaining tissue 23.1 +/- 5.3 pmol/g wet weight) and the stomach (7.1 pmol/g wet weight). The two activities gave similar curves for inhibition of beta-Ep radioimmunoassay of synthetic beta-Ep. On gel-filtration chromatography of a duodenal extract, two components of beta-EpLI were separated. When human duodenal mucosa was perfused with a solution of pH2 or 1mM or 5mM taurocholate, the release of beta-EpLI from mucosa into the perfusate increased 2-4 fold. These results indicate that beta-EpLI present in human duodenal is released by the direct action of low pH or taurocholate on the duodenal mucosa and suggest that it may have a physiological role.     

Effects of the synthetic PGE1 derivative misoprostol on basal, stimulated and nocturnal acid secretion in duodenal ulcer cases. Mechanism of action

We studied the antisecretory effect of the synthetic PGE1 derivative misoprostol. Basal, histamine-stimulated and nocturnal acid secretion were determined on separate days in 3 groups of endoscopically confirmed duodenal ulcer patients. Misoprostol or placebo were given in random order in doses of 200, 400 and 800 mcg. H+ concentration, acid output and pH of gastric content were determined. Additionally, the effect of misoprostol on purified and gastric mucosa carbonic anhydrase was determined according to Maren's micromethod. Misoprostol reduced dose-dependently basal acid secretion (by 54% after 200 mcg, by 82% after 400 mcg and, respectively, by 94% after 800 mcg) as well as stimulated secretion which was reduced after the same doses by 22% (p less than 0.05), 48% and 64% (p less than 0.001), respectively. Nocturnal secretion was significantly reduced for a period of 4 h, with a consecutive rise of gastric pH. In vitro, misoprostol inhibited dose-dependently purified and gastric mucosa carbonic anhydrase basal activity. In conclusion, misoprostol inhibits basal, nocturnal and histamine-stimulated secretion in duodenal ulcer patients, an effect which could be mediated by inhibition of carbonic anhydrase.     

Role of histamine H2-receptors in gastric and pancreatic release of somatostatin-like immunoreactivity during the gastric phase of a meal

The present study was designed to determine the role of H₂-receptors in the postprandial release of somatostatin-like immunoreactivity (SLI) from the gastric fundus and antrum and from the pancreas. In dogs subjected to laparotomy, the pylorus was bisected and a gastric fistula was created, following which 250 ml 20% liver extract (LE) at pH 7 or 2 were instilled intragastrically. In the fundic vein the incremental SLI rise in response to LE at pH 7 was 2423 ± 540 pg/ml during a control infusion of saline and 4780 ± 863 pg/ml during the infusion of cimetidine (1 mg/kg per h) (P < 0.05). In the antral vein the incremental SLI in response to LE at pH 7 was 2182 ± 530 pg/ml during the saline control but did not rise significantly during cimetidine infusion. In the pancreatic vein the incremental SLI level after LE at pH 7 was 1953 ± 358 pg/ml in the control experiments and 4430 ± 1024 pg/ml during cimetidine infusion (P < 0.025). The incremental inferior vena cava SLI level was approximately 925 pg/ml in both groups (not significant).The instillation of LE at pH 2 during the saline control lowered fundic vein SLI by 500 pg/ml; this decline was abolished during cimetidine infusion. In the antral vein the incremental SLI level of 15 750 ± 2514 pg/ml during saline was lowered to only 6728 ± 2257 pg/ml during cimetidine (ifP < 0.025). After LE at pH 2 the incremental pancreatic vein SLI level of if5641 ± to be one regulatory component in the modulation of gastric acid secretion and gastrin release [21,26] during the gastric phase of a meal. The possible involvement of H₂-receptors in this regulatory system is schematized in Fig. 7.Pancreatic SLI release is also influenced by H₂-receptors but this appears to depend on the intragastric pH; stimulation of the receptors appears to lower the pancreatic SLI response to neutral protein and raise the response to acidified protein. If these effects are due to stimulation of gastric and/or pancreatic H₂-receptors can not be determined from the present data.These findings, in conjunction with previous studies [21–25], reveal a highly complex regulatory system for somatostin release during the gastric phase of meal, and indicate that, in addition to the influence of muscarinic-cholinergic [23], adrenergic mechanisms [24] and prostaglandins [25], reveal a histaminergic influence must now be recognized.     

Vagotomy for Gastric Ulcer

Out of a series of 75 patients who were treated by vagotomy and drainage for gastric ulcer 66 have been followed up for one to seven years (average three-and-a-half years). Four recurrent gastric ulcers occurred among the 33 cases of ulcer of the lesser curve or body with no antral or duodenal lesion (type I). Among the 42 patients with an antral ulcer or an associated active or healed pyloric or duodenal lesion (type II or III) there was only one recurrence. The recurrence rate for men was 5% and for women 12%. One patient died two years after operation from cancer which may have originated in the stomach. The clinical results in patients without recurrences were generally satisfactory.Vagotomy, preferably selective, with drainage is a satisfactory operation in gastric ulcers of types II and III. For ulcers of type I, gastrectomy is to be preferred except in selected cases.     

Translocation of MAP (Erk-1 and -2) kinases to cell nuclei and activation of c-fos gene during healing of experimental gastric ulcers.

We examined localization of extracellular signal regulated kinases (Erk) 1 and 2, and c-fos mRNA expression in normal and ulcerated gastric mucosa in rats at 1, 3 and 7 days after gastric ulcer induction. In normal gastric mucosa immunofluorescence signal for Erk-1 and Erk-2 was detectable in surface epithelial, neck and some glandular cells. In gastric mucosa of the ulcer margin, almost all epithelial cells displayed strong Erk-1 and Erk-2 immunoreactivity in the basolateral membranes and the cytoplasm. In addition 19+/-3% of cells showed nuclear localization of the Erk-1 and -2 signal. The c-fos mRNA expression was increased by 790+/-14% and 220+/-10%, respectively in gastric ulcer at 3 and 7 days after ulcer induction. Since in in vitro models nuclear translocation of Erk-1 and -2 triggers cell proliferation, our finding indicates relevance of this mechanism to gastric ulcer healing.     

Peptide YY interacts with secretin and duodenal acidification to inhibit gastric acid secretion

Previous studies have indicated that plasma levels of peptide YY (PYY) increase significantly after a meal. The purpose of this study was to characterize the interaction of PYY and secretin in the inhibition of gastric acid secretion, and to determine whether PYY can influence acid-induced inhibition of gastric acid secretion in conscious dogs. I.v. administration of PYY at 200 pmol/kg/h inhibited pentagastrin (1 microgram/kg/h)-stimulated gastric acid output (P less than 0.05). PYY further augmented i.v. secretin-induced inhibition of pentagastrin-stimulated gastric acid output by 32 +/- 7%, and intraduodenal hydrochloric acid-induced inhibition of pentagastrin-stimulated gastric acid output by 40 +/- 12%. The mean integrated release of secretin response to duodenal acidification (3.9 +/- 1.0 ng-[0-60] min/ml) was not affected by PYY (3.3 +/- 0.9 ng-[0-60] min/ml). The present study demonstrates that PYY can interact with secretin and duodenal acidification in an additive fashion to inhibit pentagastrin-stimulated gastric acid secretion. Our results suggest that several hormones that are released postprandially can interact with each other to inhibit gastric acid secretion.     

Marked increase in gastric histidine decarboxylase activity in patients with hypergastrinemia.

Histidine decarboxylase (HDC) activity and histamine content were measured in endoscopic gastric biopsy specimens of 19 control subjects with normogastrinemia and 6 patients with hypergastrinemia. In controls, the HDC activity was 3 fold higher in fundic mucosa (120 +/- 13 fmol/min/mg protein, mean +/- S.E.) than in antral mucosa (39 +/- 5 fmol/min/mg protein). In patients with hypergastrinemia, an extremely high HDC activity (713 +/- 181 fmol/min/mg protein) was observed in fundic mucosa, although the HDC activity in antral mucosa was not significantly different from that of controls. The histamine content in fundic mucosa was also significantly higher in patients with hypergastrinemia than in controls but no significant difference was seen in histamine content in antral mucosa between the two groups. These results are compatible with the hypothesis that in man, as well as in rat, histamine synthesis in fundic mucosa is enhanced by gastrin.     

Occurrence of Campylobacter pylori in gastric mucosa and selected parameters of cell-mediated immunity in patients with duodenal ulcer and individuals with non-ulcerative dyspepsia]

The study was aimed at investigating a relationship between Campylobacter pylori infection in the gastric mucosa and selected parameters of cell-mediated immunity in patients with duodenal ulcer and the individuals with non-ulcerative dyspepsia. A relationship between Campylobacter pylori and gastritis has also been studied. Endoscopic and immunological tests were carried out in the group of 45 patients, including 14 patients with duodenal ulcer and 29 with non-ulcerative dyspepsia. Specimens of gastric mucosa were collected endoscopically for histological and bacteriological examinations. Immunological tests included an assessment of the number of lymphocytes T (and their subpopulations) forming active rosettes (ARFC); total - (TRFC) and theophylline-resistant in active rosettes fraction (ARFC-TR); total (TRFC-TR) and theophylline-sensitive lymphocytes in both fractions (ARFC-TS and TRFC-TS) in 1 mm3 of the peripheral blood. Results suggest, that there is correlation between an infection of the gastric mucosa by Campylobacter pylori and duodenal ulcer and gastritis. No correlation between the infection by Campylobacter pylori and examined parameters of immunity in both patients with duodenal ulcer and non-ulcerative dyspepsia was found.     

The microflora of ulzerous zone mucosa in patients with duodenal ulcer

Bacteriological study of the biopsies taken from gastric and duodenal mucosa of 10 healthy volunteers and 74 patients with duodenal ulcer, was carried out. In the gastroduodenal zone of healthy subjects microorganisms of 6 genera (Streptococcus, Candida, Staphylococcus, Bacillus, Helicobacter and Lactobacillus) were detected. H. pylori was isolated in 20% of cases only in biopsy specimens taken from the antral section of the stomach of healthy as monoculture or in combination with C. albicans. In patients with duodenal ulcer activation of opportunistic microflora was observed in the periulcerous zone. More often H. pylori occurred in associations with fungi of the genus Candida, streptococci, staphylococci, enterobacteria, Pseudomonas and other microorganisms (of more than 30 genera). Quantitatively the dominating microorganisms (3.8-5.7 lg CFU/g) were H. pylori, fungi of the genus Candida, bacteria of the genera Streptococcus, Peptostreptococcus, Bacteroides, Gemella, Prevotella, Veillonella, Peptococcus, Bacillus, different species of opportunistic enterobacteria, as well as bacteria of the genera Staphylococcus, Micrococcus, Corynebacterium, Neisseria, Pseudomonas, etc. Opportunistic bacteria detected in the ulcerous zone, as a rule, expressed hemolytic, lecithinase, RNAase, caseinolytic, catalase and urease activity. Sonicated filtrates of such cultures produced a cytotoxic effect on cells HEp-2. Ulcer is an infected wound that needs sanitation.     

Beta-adrenergic stimulation of gastrin release mediated by gastrin-releasing peptide in rat antral mucosa

The present studies were directed to examine the effects of beta-adrenergic and cholinergic stimulation on gastrin release and to assess the potential role of gastrin-releasing peptide in exerting these effects, utilizing incubated rat antral mucosa. Rat antral mucosa was incubated at 37 degrees C in Krebs-Henseleit bicarbonate buffer, pH 7.4, continuously gassed with 95% O2-5% CO2. After 1 h media were sampled for radioimmunoassay measurement of gastrin content. Inclusion of carbachol (2.5 X 10(-6) M) in culture medium increased medium gastrin concentration by 106 +/- 28% (P less than 0.01); addition of specific antibodies to gastrin-releasing peptide to the culture medium did not affect carbachol-stimulated gastrin release. Inclusion of isoproterenol (10(-9) M) in culture medium did not affect somatostatin release into the medium, but increased medium gastrin by 234 +/- 24% (P less than 0.001). However, in contrast to carbachol, addition of antibodies to gastrin-releasing peptide to culture medium decreased isoproterenol-stimulated gastrin release by 67 +/- 9% (P less than 0.001). Results of these studies indicate that, under the conditions of these experiments, beta-adrenergic, but not muscarinic, stimulation of gastrin release may be mediated, at least in part, through gastrin-releasing peptide.     

幽门弯曲菌与慢性胃炎和消化性溃疡关系的系列研究

我院自1986年6月至1989年6月检查了634例病人的胃粘膜,从幽门弯曲菌(CP)的细菌学、致病性、病理学、诊断方法及药物治疗等方面进行了研究,探讨CP与慢性胃炎及消化性溃疡的关系。结果发现CP有两种形态并与空弯菌不同,不产生肠毒素;消化性溃疡的CP检出率为80.9％,慢性胃炎为41.6％,显著高于正常胃粘膜(3.7％);CP与消化性溃疡、慢性胃炎,十二指肠炎特别是活动性炎症有密切关系;CP对胃型上皮或粘液有某种亲和性;观察到上皮细胞破溃处有大量细菌聚集,CP有致细胞病变的能力。用阿的平代替吖啶橙荧光染色,并制成CP感染快速诊断试剂盒。呋喃唑酮促进溃疡愈合,使45～73％病例CP消失,50～70％胃炎好转。但有复发,根除CP有困难。