Gastrin and the vagus interact in the trophic control of the rat oxyntic mucosa

Gastrin is a trophic hormone for the stomach, and permanent reduction of circulating gastrin by antrectomy leads to atrophy of the oxyntic mucosa, including a reduced density of histamine-storing endocrine cells (so-called ECL cells). Recently, it was proposed that also the vagal nerve has a trophic influence on the stomach. The two vagal trunks innervate the anterior and posterior side of the gastric wall, respectively. This arrangement makes it possible to denervate one side of the stomach selectively. The objective of the present study was to examine the consequences of combined antrectomy and vagotomy (unilateral or bilateral). Male Sprague-Dawley rats were subjected to unilateral or bilateral subdiaphragmatic truncal vagotomy with or without antrectomy. Control rats were sham-operated. The rats were killed 8 weeks after the operation. Bilateral vagotomy raised the basal serum gastrin concentration (fasting level). The thickness of the oxyntic mucosa and the density of ECL cells were not significantly different from age-matched vagally intact controls. Unilateral vagotomy induced no change in the basal serum gastrin concentration, nor did it affect the mucosa on the intact side. On the denervated side, however, there was reduced mucosal thickness and a greatly reduced ECL cell density. With a combination of antrectomy and vagal denervation the decrease in ECL cell density was exaggerated compared to the effect of antrectomy or unilateral vagotomy alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Rapid onset of (R)-α-methylhistamine protection in response to ethanol-induced histologic damage in rat gastric mucosa

The influence of pretreatment with (R)-α-methylhistamine, selective agonist of histamine H₃ receptors, has been investigated on gastric mucosal lesions at different time intervals, from 5 to 60 minutes, after administration of absolute ethanol in the rat. The amount and depth of lesions were quantitatively evaluated by light microscopy. In rats pretreated with (R)-α-methylhistamine, the integrity of the mucosa was preserved in approximately 80% of the total mucosal length measured despite ethanol challenge. Prevention of lesion formation was as great at 5 min after ethanol administration as at 60 min. When present, damage involved mainly superficial mucosa and lesions extending deeply into the gland region were evident in 1–2.5% of the total mucosa. Present findings indicate that mechanisms by which (R)-α-methylhistamine operates enable the mucosa to counteract damage just from the moment of exposure to ethanol and that protection is exerted both on surface and pit cells and on gastric glands.     

Effect of low pH on the morphology and viability of Cryptosporidium andersoni sporozoites and histopathology in the stomachs of infected mice

The genus Cryptosporidium includes many common parasites infecting animals and humans, and is a major cause of diarrheal illness worldwide. The biology of gastric Cryptosporidium spp., including replication in the stomach, has not been well documented. This study evaluated the viability of Cryptosporidium andersoni sporozoites in gastric environments after excystation and examined the endogenous development and histopathological changes in the stomachs of infected mice, using a novel type of C. andersoni. Sporozoites were affected by low pH (61.6% viability after 3h at pH2.0). Electron microscopy revealed developmental parasites on the gastric foveolae but not on the surface of the gastric mucosa. Histopathological examinations at 1, 2, 4 and 12 weeks p.i. uncovered three different lesions. The gastric mucosa of foveolae filled with parasites was extended and the amount of neutral mucopolysaccharide at the mucosal surface was decreased with the first type of lesion. The gastric mucosa was atrophied, some gastric glands were disrupted and the amount of acid mucopolysaccharide at the mucosal surface was increased with the second type. Finally, the gastric mucosa was slightly extended and goblet cells were present in the gastric mucosa, indicating intestinal metaplasia, in the third type. No parasites were detected in these areas with increased acidic mucin and indications of metaplasia. The results suggest that C. andersoni parasites could not survive in acidic environments for a long period before invading host cells and preferentially develop in neutral sites of the gastric mucosa, resulting in histopathological changes and chronic shedding of oocysts.     

Effect of diacarb on the carbonic anhydrase activity in the blood and gastric mucosa and pepsinogen concentration in the gastric mucosa of the rat

It was established that the activity of blood and gastric mucosa carboanhydrase increased after the introduction of food irritant (milk) into the stomach, as well as after the subcutaneous injection of histamine. This was accompanied by the increase of pepsinogen content in the gastric mucosa. When introduced into the stomach before the food irritant or histamine, acetazolamide inhibited blood and gastric mucosa carboanhydrase and reduced the content of pepsinogen in the gastric mucosa. Oral administration of acetazolamide for 5 days resulted in a more remarkable inhibition of blood and gastric mucosa carboanhydrase and in a drastically reduced content of pepsinogen in the gastric mucosa. The rate of pepsinogen biosynthesis by the gastric mucosa seems to depend on the activity of carboanhydrase in blood and in the gastric mucosa.     

Quantitative ultrastructural studies on rat gastric zymogen cells under different physiological and experimental conditions

Summary Quantitative electron microscopical measurements performed on gastric zymogen cells were aimed at determinations of size and volume density of the zymogen granules, and size of cell and nuclear profiles. 17 groups of rats each comprising 6–8 animals were investigated: five of these groups were used to study the influence of fasting and feeding, three groups were killed at different intervals after a pilocarpine injection, and four other groups were investigated after an atropine injection. The remaining five groups of rats were operated on: vagotomy was performed on one group, vagotomy + pyloroplasty on another, pyloroplasty on the third group, and antrectomy on the last two groups. The operated rats were sacrificed 4 or 10 weeks after the operations.Pilocarpine was more effective than feeding in reducing the size and the amount of zymogen granules. After atropine the size and amount of zymogen granules tended to increase. Ten weeks after pyloroplasty, vagotomy + pyloroplasty, or antrectomy the mean size of the zymogen cells was reduced.Loss of trophic vagal impulses, duodenal regurgitation, and abnormal serum gastrin levels are factors which might be responsible for the zymogen cell hypotrophy in operated rats.Supported by grants from the Swedish Medical Research council (project no 12X-2298), M. Bergvalls Stiftelse, and Julins Fond. Excellent technical assistance was provided by Mrs. Sigrid Kilter and Miss Ulla Hedlund     

Persisting chronic gastritis and elevated Helicobacter pylori antibodies after successful eradication therapy

AIM: The persistence of chronic inflammation in gastric mucosa and elevated Helicobacter pylori antibodies after successful eradication therapy are common findings in clinical practice. We studied their possible association with each other and disappearance in long-term follow up, as well as their possible connection with gastric atrophy. PATIENTS AND METHODS: The study population consisted of 108 dyspeptic patients with successful eradication therapy median 6.4 years earlier. The patients underwent gastroscopy, and biopsies from antrum and corpus were evaluated by an experienced pathologist. Serum samples collected from 77 patients were studied for H. pylori antibodies, parietal cell antibodies, as well as for pepsinogen I, pepsinogen II, and gastrin-17 levels. RESULTS: The prevalence of chronic gastric inflammation and elevated H. pylori antibodies after successful eradication therapy decreased by time, but still after 5 years, 17 of 51 (33%) subjects had elevated H. pylori antibodies and 14 of 68 (21%) had a mild inactive chronic inflammation in gastric mucosa. In patients with and without chronic inflammation in gastric mucosa, elevated H. pylori antibodies were detected in three of 10 (30%) and 14 of 41 (34%), elevated parietal cell antibodies in one of 10 (10%) and six of 41 (15%), low pepsinogen I in one of 10 (10%) and none of 41, and elevated gastrin-17 in three of 10 (30%) and six of 41 (15%), respectively. CONCLUSION: More than 5 years after successful H. pylori eradication therapy, mild persistent chronic inflammation may occur in gastric mucosa in up to one-fifth and elevated H. pylori antibodies even in one-third of patients, although these two are independent phenomena.     

Immunohistochemical detection of metallothionein in carcinomatous and normal human gastric mucosa

Utilising a specific monoclonal mouse antibody (E9), metallothionein (MT) expression has been immunohistochemically investigated in 112 formalin-fixed paraffin-embedded surgical gastric samples, 38 of which were early carcinomas (EGC) and 74 advanced ones (AGC); clinico-pathological details and follow-up data (ranging from 3 to 197 months, mean 60.5 months) were available. Eighty-nine portions of gastric mucosa adjacent to examined carcinomas (transitional mucosa) were also analysed; in addition, 22 biopsies of normal gastric mucosa were studied as tissue control. The MT immunoreactivity was evaluated by staining and intensity-distribution scores. A various MT positivity was appreciable in the cytoplasm and nucleus of antrum or body gastric epithelial cells in 100% of normal control biopsies. 75/112 (67%) gastric carcinomas showed MT immunoreactivity with a significant lower expression in AGC. No relationships were encountered between MT immunostaining and clinico-pathological data; in addition, no difference in the Kaplan-Meier survival curves of patients with various MT expression was achieved. When the transitional mucosa was examined, 84/89 (94%) samples were stained although the immunoreaction was not always concordant with that encountered in adjacent carcinomatous elements. The significant statistical decrease of MT scores observed by us moving from normal to neoplastic gastric mucosa allows us to exclude the hypothesis of an overexpression of MT in gastric carcinomas.     

Synchronization of proliferating cells in the liver, gastric glands and duodenum

Multiple injections (5-6 times) of hydroxyurea to hepatectomized rats lead to synchronization of 78% of proliferating cells in the regenerating liver. The amount of DNA-synthesizing cells of the foveolar epithelium of the pyloric glands of the gastric mucosa increases 2.7-fold, the proliferation in slowly renewing Brunner glands of the duodenum is dramatically activated.     

Morphologic, biochemical and functional properties of the mitochondria of the rabbit gastric mucosa]

Purified fractions of the rabbit gastric mucosa and liver mitochondria were isolated. Electrone microscopy and functional studies of mitochondria showed the most intact mitochondria of gastric mucosa to be localized in gradient fractions of p=1.16-1.18, and those of the liver in fractions with p=1.19-1.20. The gastric mitochondria differed from the liver mitochondria by specific localization in oxyntic cells, abundance of crists, small matrix volume, presence of high respiratory control at lesser values of pH, high respiratory activity, great amount of cytochromes of electron transport chain in inner mitochondria membrane, two-fold excess of cytochroma a in relation to b and c, absence of b5 and by presence of great amount of phosphathydilaethanolamine and unsaturated fatty acids.     

Effect of acute surgical vagotomy on the mucosal content of 6-keto-PGF1 alpha, PGE2 and glutathione after intragastric 96% ethanol treatment in rats.

It has been observed earlier that gastric cytoprotection produced by PGI2, beta-carotene, small doses of atropine or cimetidine has failed in surgically vagotomized rats. This phenomenon may be in connection with endogenous prostaglandins (PGs) and glutathione (GSH) level of the gastric mucosa. The aims of the study were to evaluate the effect of vagus nerve on the gastric mucosal 6-keto-PGF1 alpha, PGE2 and glutathione after intragastric 96% ethanol (ETOH) treatment. The observations were carried out on CFY rats. The gastric mucosal damage was produced by intragastric administration of 1 ml 96% ETOH. Acute bilateral surgical vagotomy (ASV) was carried out 30 min prior to ETOH application. The animals were sacrificed 1, 5, 15 or 60 min after ETOH installation. The number and the severity of gastric mucosal lesions were noted and 6-keto-PGF1 alpha, PGE2 an GSH contents of gastric mucosa were measured. It has been found that: 1. the number and the severity of gastric mucosal lesions were increased after ASV compared to those with intact vagal nerve, 2. 96% ETOH treatment increased both the gastric mucosal PGs and GSH levels, 3. 6-keto-PGF1 alpha peaked at 5 min PGE2 and GSH peaked at 15 min after ETOH treatment, 4. ASV decreased the gastric mucosal PGs content and delayed the peaks of PGE2 and GSH. It has been concluded that the decreased content of PGs and the delayed GSH increase may play a pathological role in the failure of gastric cytoprotection of rats after ASV.     

Five- to Eight-year Results of Truncal Vagotomy and Pyloroplasty for Duodenal Ulcer

From January 1963 to December 1965 inclusive 192 men with duodenal ulcer were treated by elective truncal vagotomy and pyloroplasty with one death. Ten subsequent deaths were due to causes unrelated to the ulcer or operation, and 17 patients became untraceable. The remaining 164 patients have been followed up for five to eight years. The late results have been compared with those obtained in a previous study of patients five to eight years after truncal vagotomy and gastroenterostomy, truncal vagotomy and antrectomy, and subtotal gastrectomy respectively for duodenal ulcer.Of the various postgastric operation syndromes early dumping, late dumping, bilious vomiting, and diarrhoea were all less frequent, but not significantly so, after vagotomy and pyloroplasty than after vagotomy and gastroenterostomy.Recurrent ulceration was commoner after vagotomy and pyloroplasty than after all the other operations, the incidence of proved and suspected recurrent ulcers being respectively 6·7 and 7·3% after vagotomy and pyloroplasty, but only 2·5 and 5·9% after vagotomy and gastroenterostomy, 0 and 5·2% after vagotomy and antrectomy, and 0·9 and 3·7% after subtotal gastrectomy. The differences between vagotomy and pyloroplasty and vagotomy and antrectomy or subtotal gastrectomy are statistically significant, but those between vagotomy and pyloroplasty and vagotomy and gastroenterostomy are not.Overall assessment (Visick grading) of the outcome gave poorer results after vagotomy and pyloroplasty than after any other operation, with 14% of category IV cases after vagotomy and pyloroplasty, 11% after vagotomy and gastroenterostomy, 8% after vagotomy and antrectomy, and 6% after subtotal gastrectomy—differences that are significant between vagotomy and pyloroplasty and vagotomy and antrectomy or subtotal gastrectomy but not between vagotomy and pyloroplasty and vagotomy and gastroenterostomy.In the light of these findings it is suggested that truncal vagotomy and pyloroplasty has not lived up to expectations and its place as the currently most popular procedure in the elective surgical treatment of duodenal ulcer should be reconsidered.     

白术配伍人参前后挥发油调控慢性萎缩性胃炎大鼠AQP 3、4表达的比较研究

为探究参术药对配伍治疗慢性萎缩性胃炎的增效机制,本文就白术配伍人参前后挥发油成分物质基础变化及对慢性萎缩性胃炎大鼠胃组织水通道蛋白3(AQP 3)、水通道蛋白4(AQP 4)的影响进行了比较研究。采用水蒸气蒸馏法提取人参白术配伍前后挥发油,以GC-MS法表征挥发油化学特征,并随机将大鼠分成空白组、模型组、白术挥发油组及配伍挥发油组,使用MNNG建立慢性萎缩性胃炎模型,给药后观察各组胃黏膜组织显微、超微结构变化以及AQP 3、AQP 4的表达。结果显示,白术配伍人参后挥发油的提取量升高,经GC-MS测定,配伍后苍术酮相对含量降低,新增少量人参挥发油成分。显微及超微观察显示,模型组大鼠胃组织黏膜折叠皱起,黏膜层和固有层腺体萎缩严重,胃小凹形态改变,上皮细胞破损,炎症细胞大面积浸润,且病理评分明显高于正常组(P<0.05);各药物组与模型组相比,均缓解或改善上述病理结果,且配伍挥发油组表现更优。免疫组化结果显示,模型组大鼠胃黏膜AQP 3、AQP 4表达明显低于空白组(P<0.05);相较模型组,各药物组对胃黏膜AQP 3、AQP 4蛋白的表达有增加趋势或明显增加,且配伍挥发油组...     

Effects of ethanol on gastric acid secretion and gastric mucosal cyclic AMP in the rat.

The effect of ethanol on the secretion of gastric acid and the content of cyclic AMP of the gastric mucosa was studied in rats. Intravenously, ethanol (10 to 800 mg/kg) had no effect on the output of acid. Upon local application into the stomach, ethanol (1 to 10%) caused a concentration-dependent inhibition of the output of gastric acid. The effect was evident within 5 min. At the concentration of 1 %,ethanol decreased the rate of acid secretion maximally by about 30%. At the concentration of 3 %, the maximal inhibition was about 70 %. At the concentration of 10 %, ethanol caused a total cessation of the output of acid within 20 to 60 min.Five and 25 min after the administration of 10 % ethanol into the stomach, the gastric mucosal content of cyclic AMP was decreased by approximately 50 %. Also in vitro, the mucosal content of cyclic AMP was decreased by ethanol within 5 min. The decrease was about 30 % with 2.5 % ethanol, approximately 60 % with 10 % ethanol, and approximately 45 % with 20 % ethanol. Alcohol inhibited the activity of the cyclic AMP phosphodiesterase of the gastric mucosa in a competitive manner. The K_i-value was 0.16 M which would correspond to an alcohol concentration of 9.1 % (v/v). Ethanol caused a concentration-dependent inhibition of the activity of the gastric mucosal adenyl cyclase. By 0.166 M (9.4 %) alcohol the inhibition was nearly 100 %.It is concluded that the ethanol-induced decrease of cyclic AMP in the gastric mucosa is due to a decreased formation of the nucleotide. The accompanying inhibition of the output of acid by ethanol is consistent with the view that cyclic AMP is an intracellular regulator of the gastric acid secretion. In view of the role of cyclic AMP in the control of the integrity of the cells, it is suggested that the ethanol-induced damage of gastric mucosa might also be, at least partly, due to the decreased mucosal content of cyclic AMP.     

Remodeling of the Residual Gastric Mucosa after Roux-En-Y Gastric Bypass or Vertical Sleeve Gastrectomy in Diet-Induced Obese Rats

Whereas the remodeling of intestinal mucosa after bariatric surgeries has been the matter of numerous studies to our knowledge, very few reported on the remodeling of the residual gastric mucosa. In this study, we analyzed remodeling of gastric mucosa after Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) in rats. Diet-induced obese rats were subjected to RYGB, VSG or sham surgical procedures. All animals were assessed for food intake, body-weight, fasting blood, metabolites and hormones profiling, as well as insulin and glucose tolerance tests before and up to 5 weeks post-surgery. Remodeling of gastric tissues was analyzed by routine histology and immunohistochemistry studies, and qRT-PCR analyses of ghrelin and gastrin mRNA levels. In obese rats with impaired glucose tolerance, VSG and RYGB caused substantial weight loss and rats greatly improved their oral glucose tolerance. The remaining gastric mucosa after VSG and gastric pouch (GP) after RYGB revealed a hyperplasia of the mucous neck cells that displayed a strong immunoreactivity for parietal cell H⁺/K⁺-ATPase. Ghrelin mRNA levels were reduced by 2-fold in remaining fundic mucosa after VSG and 10-fold in GP after RYGB. In the antrum, gastrin mRNA levels were reduced after VSG in line with the reduced number of gastrin positive cells. This study reports novel and important observations dealing with the remaining gastric mucosa after RYGB and VSG. The data demonstrate, for the first time, a hyperplasia of the mucous neck cells, a transit cell population of the stomach bearing differentiating capacities into zymogenic and peptic cells.     

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.     

Suppressive effect of astaxanthin isolated from the Xanthophyllomyces dendrorhous mutant on ethanol-induced gastric mucosal injury in rats

Ethanol has been found to induce ulcerative gastric lesion in humans. The present study investigated the in vivo protective effect of astaxanthin isolated from the Xanthophyllomyces dendrorhous mutant against ethanol-induced gastric mucosal injury in rats. The rats were treated with 80% ethanol for 3 d after pretreatment with two doses of astaxanthin (5 and 25 mg/kg of body weight respectively) for 3 d, while the control rats received only 80% ethanol for 3 d. The oral administration of astaxanthin (5 and 25 mg/kg of body weight) showed significant protection against ethanol-induced gastric lesion and inhibited elevation of the lipid peroxide level in gastric mucosa. In addition, pretreatment with astaxanthin resulted in a significant increase in the activities of radical scavenging enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. A histologic examination clearly indicated that the acute gastric mucosal lesion induced by ethanol nearly disappeared after pretreatment with astaxanthin.     

Normalization of phospholipids concentration of the gastric mucosa was observed in patients with peptic ulcer after eradication of Helicobacter pylori

Background. Phospholipids concentration in the gastric mucosa decreased in patients with Helicobacter pylori infection. The aim of this study is to examine the effects of eradication of H. pylori on decreasing the phospholipids concentration in the gastric mucosa in patients with gastric or duodenal ulcer. Materials and Methods. Phospholipids (phosphatidylcholine, phosphatidylethanolamine, and sphingonomyeline) were measured in biopsy specimens from the antrum and corpus using thin‐layer chromatography. In H. pylori positive patients with gastric ulcer (n = 26) and duodenal ulcer (n = 13), and H. pylori negative controls (n = 20), the biopsy specimens were obtained before and 3 months after eradication. Eradication was performed using lansoprazole, amoxycillin, and clarithromycin. Results. Compared with the H. pylori negative control group, the concentrations of phosphatidylcholine and phosphatidylethanolamine decreased significantly in the gastric ulcer group in both antrum and corpus mucosa, and in the duodenal ulcer group in antrum mucosa. This decrease returned to the control level after eradication. Conclusions. This study demonstrates that the eradication of H. pylori in patients with peptic ulcer normalized the decrease of phosphatidylcholine and phosphatidylethanolamine in the gastric mucosa.     

Progesterone metabolism in the gastric mucosa microsomes of guinea pig

The microsomes from guinea pig gastric mucosa were found to convert [4-14C]progesterone to two major metabolites in the presence of NADPH. The gastric metabolizing activity was the highest among the gastrointestinal tissues of guinea pig. 5 alpha-Pregnane-3,20-dione and 3 beta-hydroxy-5 alpha-pregnan-20-one were identified as the major metabolites by thin-layer chromatography and crystallization to constant specific activity, suggesting the presence of steroid 5 alpha-reductase and 3 beta-hydroxysteroid dehydrogenase activities in the gastric mucosa microsomes. Furthermore, time course of progesterone metabolism and analysis of 5 alpha-pregnane-3,20-dione metabolites suggest that the gastric progesterone metabolism is initiated by 5 alpha-reductase and followed by 3 beta-hydroxysteroid dehydrogenase. The progesterone-metabolizing activity was strongly inhibited by SKF 525-A and disulfiram. The activity was also inhibited by methyrapone to a somewhat lesser extent than the above inhibitors. From gastric mucosa microsomes, the progesterone-metabolizing activity was successfully solubilized with 2% digitonin using 0.1 M potassium chloride and 1 mM dithiothreitol, 0.4 mM NADPH and 20% glycerol as stabilizers for the solubilized activity. Among these stabilizers, glycerol was found to be most effective for stabilizing the activity of the solubilized microsomes.     

Cellular energy systems and reserpine ulcer in rats

Gastric ulcer was elicited in rats by reserpine (5 mg x kg-1 sc.) administration. Ulcer formation (number and severity) was measured 6, 12, 18 and 24 hr after reserpine administration. At the time of killing of the animals, tissue levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), cyclic adenosine monophosphate (cAMP) were measured enzymatically and by radioimmunoassay in the gastric fundal mucosa. The sum of ATP + ADP + AMP (adenylate pool) and the ratio of ATP x ADP-1 were calculated. It was found that (1) the tissue levels of ATP, AMP, cAMP, sum of ATP / ADP + AMP (adenylate pool) and ratio of ATP x ADP-1 increased significantly in the gastric fundal mucosa 6 hr after reserpine administration, thereafter these values decreased gradually and significantly; (2) the tissue level of ADP increased significantly in the gastric fundal mucosa 6 hr after reserpine administration, meanwhile its level increased significantly at 18 and 24 hr; (3) the value of energy charge (ATP + 0.5 ADP x ATP + ADP + AMP-1) remained unchanged; (4) the peaks of biochemical alterations in the gastric fundus mucosa preceded he appearance of ulcers. It was concluded that (1) reserpine ulcer appears after an active metabolic response in the rat gastric fundal mucosa; (2) hypoxaemic damage in the gastric fundal mucosa can be excluded as a possible underlying mechanism of ulcer formation produced by reserpine administration; (3) before the appearance of reserpine ulcer, significant changes in the feedback mechanism, system, i.e. between the ATP--membrane ATPase--ADP and the ATP--adenylate cyclase--cAMP energy systems, can be observed in the rat gastric fundal mucosa.