Effect of Acid Suppressants on Non-Helicobacter pylori Helicobacters Within Parietal Cells.

We investigated the effect of increased pH induced by acid suppressants on the viability of non-Helicobacter pylori helicobacters (NHPHs) within parietal cell intracellular canaliculi and fundic glandular lumina by immunohistochemistry, electron microscopy, quantitative PCR, urea breath tests, and using a bilayer culture system. Three months before the experiment, mice were infected with the NHPH H. suis and then treated with famotidine (2 mg/kg body weight [BW], once daily), lansoprazole (30 mg/kg BW, once daily), or vonoprazan (20 mg/kg BW, once daily) for 3 days. Immunohistochemical studies using the TUNEL method, quantitative PCR analysis, and urea breath tests were performed. PCR analysis showed a decrease in the NHPH quantity after vonoprazan treatment. Urea breath tests revealed a significant decrease in the NHPH urease activity after vonoprazan, lansoprazole, and famotidine treatments for 3 days; however, 4 days after the treatment, urease activity reversed to the pretreatment level for each treatment group. Electron microscopy revealed an increase in the damaged NHPH after vonoprazan treatment. The TUNEL method revealed apoptotic NHPH within parietal cells after vonoprazan treatment. The bilayer culture results demonstrated that NHPH moved more quickly at a pH of 4.0 than at a pH of 3.0, 5.0, and 6.5, and electron microscopy revealed a change from the spiral form to the coccoid form under near-neutral pH conditions. We thus proposed that acid suppressants, especially vonoprazan, induce NHPH damage by altering pH.

Inference for Convolutionally Observed Diffusion Processes.

We propose a new statistical observation scheme of diffusion processes named convolutional observation, where it is possible to deal with smoother observation than ordinary diffusion processes by considering convolution of diffusion processes and some kernel functions with respect to time parameter. We discuss the estimation and test theories for the parameter determining the smoothness of the observation, as well as the least-square-type estimation for the parameters in the diffusion coefficient and the drift one of the latent diffusion process. In addition to the theoretical discussion, we also examine the performance of the estimation and the test with computational simulation, and show an example of real data analysis for one EEG data whose observation can be regarded as smoother one than ordinary diffusion processes with statistical significance.

Coexistence of Alterations of Gastrointestinal Function and Mechanical Allodynia in the Reserpine-Induced Animal Model of Fibromyalgia.

BACKGROUND: Fibromyalgia (FM) is a disorder characterized by widespread chronic pain as core symptom and a broad range of comorbidities. Despite the prevalence of gastrointestinal (GI) comorbidities in patients with FM, GI functions have rarely been investigated in animal models of FM. AIMS: The purpose of the present study is to investigate the coexistence of alterations of GI function in the reserpine-induced myalgia (RIM) rat, a validated FM model associated with disruption of monoamine system. METHODS: Paw withdrawal threshold (von Frey hair test) was assessed as pain-associated indicator. Gastric emptying (13C breath test), small intestinal transit (charcoal meal test), and fecal water content were investigated as GI functions. RESULTS: The specific regimen of reserpine for the RIM rat, i.e., 1 mg/kg s.c., once daily for three consecutive days, caused a reduction of paw withdrawal threshold (i.e., mechanical allodynia) on days 3, 5, and 7 after the first injection. The 13CO2 excreted from the RIM rat was significantly increased on day 7. The RIM rat exhibited an acceleration of small intestinal transit on day 5. Fecal water content collected from the RIM rat was significantly increased on days 3 and 5. The amount of noradrenaline was significantly decreased in GI tissues on days 3, 5, and 7 in the RIM rat. Conclusions This study revealed that accelerated gastric emptying, accelerated small intestinal transit, and increase in fecal water content coexist with mechanical allodynia in the RIM rat, simulating the coexistence of chronic pain and alterations of GI function in patients with FM.

Structure of proliferating cell nuclear antigen (PCNA) bound to an APIM peptide reveals the universality of PCNA interaction.

Proliferating cell nuclear antigen (PCNA) provides a molecular platform for numerous protein-protein interactions in DNA metabolism. A large number of proteins associated with PCNA have a well characterized sequence termed the PCNA-interacting protein box motif (PIPM). Another PCNA-interacting sequence termed the AlkB homologue 2 PCNA-interacting motif (APIM), comprising the five consensus residues (K/R)-(F/Y/W)-(L/I/V/A)-(L/I/V/A)-(K/R), has also been identified in various proteins. In contrast to that with PIPM, the PCNA-APIM interaction is less well understood. Here, the crystal structure of PCNA bound to a peptide carrying an APIM consensus sequence, RFLVK, was determined and structure-based interaction analysis was performed. The APIM peptide binds to the PIPM-binding pocket on PCNA in a similar way to PIPM. The phenylalanine and leucine residues within the APIM consensus sequence and a hydrophobic residue that precedes the APIM consensus sequence are crucially involved in interactions with the hydrophobic pocket of PCNA. This interaction is essential for overall binding. These results provide a structural basis for regulation of the PCNA interaction and might aid in the development of specific inhibitors of this interaction.

Novel effect of α-lactalbumin on the yohimbine-induced hot flush increase of the tail skin temperature in ovariectomized rats.

5-Hydroxytryptamine (5-HT) and noradrenaline have been thought to play important roles in the mechanism of hot flush. Then, to clarify the relation between serotonergic and adrenergic nervous systems on the mechanism of hot flush, the effect of paroxetine, 5-HT reuptake inhibitor (SSRI) was evaluated on the yohimbine-induced hot flush increase of tail skin temperature in ovariectomized female rats. Yohimbine (adrenaline α2 antagonist) significantly increased the tail skin temperature in course of time. Clonidine (adrenaline α2 agonist) significantly attenuated this effect. Paroxetine also significantly inhibited the increase of tail skin temperature by yohimbine. α-Lactalbumin having SSRI activity in vitro study also significantly inhibited the increase of tail skin temperature, but not significantly decreased the initial temperature. This difference may explain the different mechanism between paroxetine (SSRI) and α-lactalbumin, suggesting new mechanism of hot flush.

The Ameliorating Effect of Lactobacillus gasseri OLL2716 on Functional Dyspepsia in Helicobacter pylori-Uninfected Individuals: A Randomized Controlled Study.

BACKGROUND/AIMS: Probiotics appear to improve Helicobacter pylori-associated dyspepsia via an inhibitory effect on H. pylori; however, uncertainty exists regarding their effects in H. pylori-uninfected individuals. We evaluated the efficacy of Lactobacillus gasseri OLL2716 (L. gasseri OLL2716) on H. pylori-uninfected individuals with functional dyspepsia (FD). METHODS: A double-blind, parallel-group, placebo-controlled, randomized, controlled trial was performed. Participants were randomly assigned to ingest L. gasseri OLL2716-containing yogurt (L. gasseri OLL2716 group) or L. gasseri OLL2716-free yogurt (placebo group) for 12 weeks. Participants completed questionnaires that dealt with a global assessment as well as symptom severity. The per-protocol (PP) population was evaluated for efficacy in accordance with a plan prepared beforehand. RESULTS: Randomization was performed on 116 individuals; the PP population consisted of 106 individuals (mean age 42.8 ± 9.0). The impressions regarding the overall effect on gastric symptoms were more positive in the L. gasseri OLL2716 group compared to that in the placebo group (statistical trend; p = 0.073). The elimination rate for major FD symptoms was 17.3 and 35.3% in the placebo and L. gasseri OLL2716 groups respectively (p = 0.048). CONCLUSION: L. gasseri OLL2716 has beneficial effects on FD without H. pylori involvement.

Bovine milk-derived α-lactalbumin prevents hepatic fibrosis induced by dimethylnitrosamine via nitric oxide pathway in rats.

The present study was designed to evaluate the hepatoprotective potential of α-lactalbumin (αLA) against dimethylnitrosamine (DMN)-induced toxic insults in the rat liver. The liver damage was induced in rats by the repeated administration of DMN (10 mg/kg, i.p.) on three consecutive days per week for three weeks. The rats were maintained on either a standard AIN-93 M or αLA-enriched diet starting one week before the DMN injection until the termination of the experiment. The DMN treatment produced a progressive increase in the plasma markers (aspartate aminotransferase, alanine aminotransferase, total bililbin, hyarulonic acid, and matrix metalloproteinase-2) in 28 days after the first DMN injection. Dietary treatment with αLA significantly reduced the DMN-induced damage toward normalcy. NＧ-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, significantly attenuated the hepatoprotective effect of αLA. These findings show that αLA has a marked suppressive effect on hepetic fibrosis through a nitric oxide-mediated mechanism.

Gastric emptying after artificial ulceration in rats: differences due to the site of the ulcer and the effects of prokinetic drugs.

Background This study aimed to evaluate the effects of the position of an acetic acid-induced gastric ulcer and the effects of prokinetic drugs on gastric emptying. Materials and Methods Male Sprague-Dawley rats were used in this study. Acetic acid ulcers were induced either in the region between the fundus and pylorus on the anterior wall of the stomach or in the glandular region on the greater curvature of the stomach to determine whether there were regional differences in the effect of the ulcers. Gastric emptying was evaluated with a breath test using [1-13C] acetic acid. In addition, the effects of the prokinetic drugs, metoclopramide and mosapride, on gastric emptying were also evaluated. Results Acetic acid induced ulcers in the region between the fundus and pylorus on the anterior wall of the stomach significantly delayed gastric emptying as compared with control rats, but not the acetic acid induced ulcers in the glandular region on the greater curvature of the stomach. Metoclopramide and mosapride did not improve the delayed gastric emptying even at doses that enhanced gastric emptying in normal rats. Conclusion These findings show that gastric emptying is influenced by the position of the ulcer and the region between the fundus and pylorus on the anterior wall plays an important role in gastric emptying. Moreover, it was found that metoclopramide and mosapride do not improve the delayed gastric emptying caused by acetic acid ulcers induced on the anterior wall in the region between the fundus and pylorus.

Correlation Between Gastric Emptying and Gastric Adaptive Relaxation Influenced by Amino Acids.

BACKGROUND/AIMS: Amino acids have many physiological activities. We report the correlation between gastric emptying and gastric adaptive relaxation using tryptophan and amino acids with a straight alkyl chain, hydroxylated chain, and branched chain. Here we sought to further clarify the correlation between gastric emptying and gastric adaptive relaxation by using other amino acids. METHODS: In Sprague-Dawley rats, gastric emptying was evaluated by a breath test using [1-13C] acetic acid. The expired 13CO2 pattern, Tmax, Cmax, and AUC120min values were used as evaluation items. Gastric adaptive relaxation was evaluated in a barostat experiment. Individual amino acids (1 g/kg) were administered orally 30 minutes before each breath test or barostat test. RESULTS: L-phenylalanine and L-tyrosine did not influence gastric emptying. All other amino acids, ie, L-proline, L-histidine, L-cysteine, L-methionine, L-aspartic acid, L-glutamic acid, L-asparagine, L-arginine, L-glutamine, and L-lysine significantly delayed and inhibited gastric emptying. L-Cysteine and L-aspartic acid significantly enhanced and L-methionine and L-glutamine significantly inhibited gastric adaptive relaxation. L-Phenylalanine moved the balloon toward the antrum, suggesting strong contraction of the fundus. Tmax showed a significant positive correlation (r = 0.709), and Cmax and AUC120min each showed negative correlations (r = 0.613 and 0.667, respectively) with gastric adaptive relaxation. CONCLUSION: From the above findings, it was found that a close correlation exists between gastric emptying and adaptive relaxation, suggesting that enhanced gastric adaptive relaxation inhibits gastric emptying.

Influence of amino acids on gastric adaptive relaxation (accommodation) in rats as evaluated with a barostat.

AIM: The present study aimed to evaluate the effects of selected straight alkyl chain, hydroxylated chain and branched chain amino acids on gastric adaptive relaxation, as these have previously been shown to have differing effects on gastric emptying. MATERIALS AND METHODS: Gastric adaptive relaxation was evaluated using a barostat in rats under urethane anesthesia. The pressure within the balloon, introduced from the mouth to the stomach, was changed stepwise from 1 to 8 mmHg. The increased volume just after the increase of balloon pressure was defined as distension-induced gastric adaptive relaxation (accommodation). Amino acids were administered orally or intravenously. RESULTS: As compared with control rats administered with distilled water, those rats that were orally administered amino acids having straight alkyl chain and extra hydroxylated alkyl chain, such as glycine and l-serine, had significantly enhanced gastric adaptive relaxation, but administration of l-alanine and l-threonine did not. Branched chain amino acids, such as l-isoleucine, l-leucine and l-valine, also did not significantly influence gastric adaptive relaxation. Glycine and l-serine showed the same efficacy when administered intravenously. CONCLUSION: Among the amino acids evaluated in the present study, glycine and l-serine significantly enhanced gastric adaptive relaxation, suggesting that short alkyl chain amino acids may enhance gastric adaptive relaxation as compared with the other amino acids. These findings may suggest that glycine and l-serine would be useful in the therapy of functional dyspepsia, especially for early satiety, because the dysfunction of adaptive relaxation is one of the causes of early satiety.

Effects of straight alkyl chain, extra hydroxylated alkyl chain and branched chain amino acids on gastric emptying evaluated using a non-invasive breath test in conscious rats.

AIM: Some amino acids been known to influence gastric emptying. Thus we have evaluated the effects of straight alkyl chain, extra hydroxylated alkyl chain and branched chain amino acids on gastric emptying. MATERIALS AND METHODS: Gastric emptying was evaluated in rats after feeding with Racol (nutrient formulae) containing [1-(13)C] acetic acid. Using a breath test, the content of (13)CO2 in their expired air was measured by infrared analyzers. Rats were orally administered with test amino acids, while control rats were administered orally with distilled water. RESULTS: The expired (13)CO2 content in the expired air increased with time, peaked after about 30 min and decreased thereafter. Among the amino acids having an alkyl chain, L-serine, L-alanine and L-glycine, significantly decreased the (13)CO2 content and Cmax, and delayed Tmax, suggesting inhibition and delay of gastric emptying. AUC(120min) values of L-alanine and L-glycine also decreased significantly. L-Threonine significantly decreased (13)CO2 content and delayed Tmax, but had no influence on Cmax and AUC(120min) values, suggesting a delay of gastric emptying. L-Isoleucine and L-leucine and L-valine significantly decreased (13)CO2 content, suggesting inhibition of the gastric emptying, but Cmax, Tmax and AUC(120min) values were not significantly affected. CONCLUSION: The results show that the amino acids used in the present study had different effects on gastric emptying. Moreover, it was found that inhibition and delay of gastric emptying were clearly classifiable by analyzing the change in (13)CO2 content of the expired air and the Cmax, Tmax and AUC(120min) values.

Amino Acid Mixture Enriched With Arginine, Alanine, and Phenylalanine Stimulates Fat Metabolism During Exercise.

Although there have been many investigations of the beneficial effects of both exercise and amino acids (AAs), little is known about their combined effects on the single-dose ingestion of AAs for lipid metabolism during exercise. We hypothesize that taking a specific combination of AAs implicated in glucagon secretion during exercise may increase fat metabolism. We recently developed a new mixture, d-AA mixture (D-mix), that contains arginine, alanine, and phenylalanine to investigate fat oxidation. In a double-blind, placebo-controlled crossover study, 10 healthy male volunteers were randomized to ingest either D-mix (3 g/dose) or placebo. Subjects in each condition subsequently performed a physical task that included workload trials on a cycle ergometer at 50% of maximal oxygen consumption for 1 hr. After oral intake of D-mix, maximum serum concentrations of glycerol (9.32 ± 6.29 mg/L and 5.22 ± 2.22 mg/L, respectively; p = .028), free fatty acid level (0.77 ± 0.26 mEq/L and 0.63 ± 0.28 mEq/L, respectively; p = .022), and acetoacetic acid levels (37.9 ± 17.7 µmol/L and 30.3 ± 13.9 µmol/L, respectively; p = .040) were significantly higher than in the placebo groups. The area under the curve for glucagon during recovery was numerically higher than placebo (6.61 ± 1.33 µg/L · min and 6.06 ± 1.23 µg/L · min, respectively; p = .099). These results suggest that preexercise ingestion of D-mix may stimulate fat metabolism. Combined with exercise, the administration of AA mixtures could prove to be a useful nutritional strategy to maximize fat metabolism.

Probiotic (yogurt) containing Lactobacillus gasseri OLL2716 is effective for preventing Candida albicans-induced mucosal inflammation and proliferation in the forestomach of diabetic rats.

Oral and esophageal candidiasis sometimes leads to mucosal hyperplasia, and progresses to carcinoma. We have produced an animal model for hyperplastic mucosal candidiasis in the forestomach that has a proliferative lesion of the squamous epithelium with chronic inflammation and C. albicans infection, some of which advanced to squamous cell carcinoma. There are many reports of the antibacterial effects of probiotics, but consensus about their antifungal effect has not been reached. In the present study, we investigate whether probiotic (yogurt) containing Lactobacillus gasseri OLL2716 (LG21 yogurt) can prevent proliferative and inflammatory changes caused by C. albicans in this mucosal candidiasis animal model. Diabetes was induced in 8-week-old WBN/Kob rats by intravenous administration of alloxan. One group of diabetic rats received a saline containing C. albicans and LG21 yogurt orally (DC+LG21 group) for 30 weeks, and another group received only C. albicans (DC group) for 30 weeks. They were sacrificed at 40 weeks of age, and analyzed histopathologically. In the DC+LG21 group, squamous hyperplasia at the greater curvature was significantly milder, and the Ki-67 positive index was significantly lower compared with the DC group. Suppurative inflammation with C. albicans also tended to be suppressed at the greater curvature. These findings suggest that probiotic (yogurt) containing Lactobacillus gasseri OLL2716 can suppress squamous hyperplastic change and inflammation associated with C. albicans infection in the forestomach.

Effects of L-tryptophan on gastric emptying evaluated by breath test in relation to gastric accommodation evaluated by Barostat in rats.

Gastric emptying has been known to correlate the pyloric sphincter contractile function and distention-induced gastric relaxation (gastric accommodation). In the present study, the effects of L-tryptophan on the gastric emptying and accommodation were evaluated by breath test using [1-(13)C]acetic acid and Barostat study, respectively, in rats. L-Tryptophan significantly decreased Cmax and AUC120min and delayed Tmax, indicating the inhibition of gastric emptying. L-Tryptophan significantly enhanced the gastric accommodation. These findings show that L-tryptophan may inhibit the gastric emptying through the enhanced gastric accommodation. Therefore, L-tryptophan may be useful for the therapy of postprandial dyspepsia, especially for early satiety.

Effect of colonic distension on gastric adaptive relaxation in rats: barostatic evaluation using an orally introduced gastric balloon.

While the gastrocolonic reflex has been known, the cologastric relationship has not been clarified especially with regard to gastric adaptive relaxation. Therefore, in this study we have examined the correlation between gastric adaptive relaxation and colonic distension. Male Sprague-Dawley rats were used after fasting for 18 hrs. Colonic distension was performed by injecting 2.2 ml of air into a colonic balloon inserted into the colon for 5 min in conscious state. After urethane anesthesia, gastric adaptive relaxation was investigated by using a slightly modified gastric balloon introduced into the stomach through the mouth. Gastric balloon volumes increased gradually just after an increment in the gastric balloon pressure (1 to 8 mmHg), and reached a plateau within 1 min. This increased volume was defined as gastric adaptive relaxation. In control rats, gastric adaptive relaxation increased with pressure increments in a pressure dependent manner. In the colon-distended rats, gastric adaptive relaxation increased also in a pressure dependent manner, but was significantly inhibited as compared with control at 8 mmHg (P<0.05). These findings show that colonic distension inhibits the gastric adaptive relaxation and suggests the existence of a cologastric relationship in rats.

Effects of Lactobacillus gasseri OLL2809 and α-lactalbumin on university-student athletes: a randomized, double-blind, placebo-controlled clinical trial.

Strenuous exercise reduces immune cell function and increases the risk of respiratory and gastrointestinal infections. In addition, it affects mood state and causes physical fatigue. Athletes require both mental and physical conditioning to execute good performance. In this study, we conducted a randomized, double-blind, placebo-controlled clinical trial to evaluate the immunopotentiation and fatigue-alleviation effects of Lactobacillus gasseri OLL2809 (LG2809) and α-lactalbumin (αLA) in university-student athletes after strenuous exercise. A total of 44 university students who performed strenuous exercise daily were separated into 3 groups to receive a 4-week course of placebo, 100 mg LG2809, or 100 mg LG2809 in combination with 900 mg αLA, respectively. Before and after each dietary treatment, the subjects performed strenuous cycle ergometer exercise for 1 h. Before and after each exercise session, blood samples and visual analogue scale scores for fatigue were obtained. In addition, the mood of each subject before and after the dietary treatment was evaluated using the Profile of Mood States (POMS) questionnaire. LG2809 ingestion was effective in preventing reduced natural killer cell activity due to strenuous exercise and elevating mood from a depressed state. In addition, LG2809 + αLA was found to alleviate minor resting fatigue, which was supported objectively by the significant reduction in the serum reactive oxygen metabolites and transforming growth factor ß1 levels. These effects could be helpful for athletes to maintain mental and physical condition.

Effects of Lactobacillus gasseri OLL2809 on the induced endometriosis in rats.

We have reported an inhibitory effect of Lactobacillus gasseri OLL2809 (OLL2809) on the growth of mouse endometrial tissue in the abdominal cavity. The present study aimed to investigate the efficacy of Lactobacillus gasseri OLL2809 (OLL2809) on pre-existing endometriosis implanted on the abdominal wall in diestrus Wistar-Imamichi female rats. One week after implantation, the volume of the endometrial tissue was measured after laparotomy. OLL2809 and dienogest were administered for 4 weeks. OLL2809 significantly enhanced the decrease in the volume (p<0.01) as compared with control. Complete healing was observed in two of nine rats, but in none of the control group. Dienogest did not show significant efficacy. These findings suggest that OLL2809 is useful not only in therapy of pre-existing endometriosis but also in the prevention of the growth of endometrial tissue.

Dual role of mosapride citrate hydrate on the gastric emptying evaluated by the breath test in conscious rats.

Mosapride citrate hydrate (mosapride) has been known to act as a 5-HT4 agonist and to enhance gastric emptying. However, its mode of action, such as time course and dosage effect, on gastric emptying has not been clarified. This study aimed to clarify these points by the breath test using [1-(13)C]acetic acid in conscious rats. Mosapride significantly and dose-dependently enhanced the gastric emptying increased Cmax and AUC120 min at doses between 0.1 and 3 mg/kg. Pre-treatment with GR113808 (5-HT4 antagonist) significantly attenuated the enhancement of gastric emptying by mosapride. On the contrary, at a dose of 30 mg/kg, mosapride significantly inhibited the gastric emptying. The major metabolite (M1: 5-HT3 receptor antagonist) significantly inhibited gastric emptying at doses of 19.2 and 64.1 mg/kg (equimolar to 30 and 100 mg/kg of mosapride, respectively), suggesting that the inhibitory effect by mosapride may be caused at least in part by the 5-HT3 receptor antagonistic effect of M1. These findings show that mosapride has dual role on the gastric emptying and may support the usefulness of mosapride for the therapy of postprandial distress syndrome such as early satiation and postprandial fullness.

Sequential observation of implanted endometriosis by laparoscopy in rats: correlation between the prevalence rate and the estrous cycle.

This study aimed to clarify the correlation between the estrous cycle and prevalence rate of endometriosis by sequential laparoscopy in Wistar-Imamichi female rats. The peritoneal implantation of endometrial tissue was performed in four estrous cycle rats (proestrus, estrus, metestrus, and diestrus). One week after implantation, the volume of the ectopic endometriosis was measured, and sequential laparoscopy was performed for 4 weeks to observe the prevalence rate. Five weeks after implantation, the volume of the ectopic endometriosis was measured again after laparoscopy. One week after implantation, the volume of endometriosis was significantly larger in proestrus and estrus rats than metestrus and diestrus rats. Prevalence rate was decreased with time. Five weeks after implantation, the prevalence rate and volume were higher and larger in the metestrus, diestrus, and estrus rats than in the proestrus rats. These results show that the estrous cycle affects the change of ectopic endometriosis. The decrease of prevalence rate was slow in metestrus, diestrus, and estrus rats as compared to that in proestrus rats. The volume of ectopic endometriosis showed little decrease with time when the endometrial tissue was implanted during the metestrus and diestrus portion of the cycle. Moreover, sequential laparoscopy made it possible to observe the prevalence rate of endometriosis.

Evaluation of adaptive relaxation of the rat stomach using an orally inserted balloon instead of surgical intervention by demonstrating the effects of capsaicin and Nω-nitro-L-arginine methylester.

Gastric functions such as adaptive relaxation have usually been monitored in rats using a surgically inserted barostat's balloon. However, surgery causes physiological damage to the rat stomach. This study is an investigation of adaptive relaxation of the rat stomach using a slightly modified balloon, which is introduced into the stomach through the mouth of anesthetized rats without the need for balloon surgery, attached to a brostat. In this case, the balloon was placed between the fore-stomach and the fundus, but towards the fore-stomach. The balloon volume increased gradually just after an increment in the balloon pressure, and reached a plateau within 1 min. This increased volume just after the increment of the balloon pressure was defined as adaptive relaxation. Adaptive relaxation increased with pressure increases in a pressure dependent manner. Pre-treatment with Nω-nitro-L-arginine methylester (30 mg/kg, i.v.) caused this adaptive relaxation to be significantly inhibited as compared with the control. On the contrary, adaptive relaxation was significantly enhanced by pre-treatment with capsaicin (0.5 mg/kg, p.o.). These findings show that this method is both useful for investigating the physiology of adaptive relaxation of the stomach without surgery and to show that nitric oxide plays an important role in the adaptive relaxation of the stomach as reported previously.