Effect of Combination Therapy of Oral Famotidine with Mosapride on Intragastric pH and Gastric Emptying in Rats

Background/Aims@#Studies in healthy humans have reported that the addition of mosapride to acid suppressants resulted in higher intragastric pH than acid suppressant administration alone. We investigated the effect of the addition of mosapride to famotidine on the intragastric pH and gastric emptying rate (GER) in rats. @*Materials and Methods@#Sixty male Wistar rats were used in this study. Experimental groups were divided into control, famotidine-only, mosapride-only, and famotidine with mosapride (combination). The first experiment was performed in non-stressed rats. Mosapride was administered by oral gavage 1 hour before the meal, and famotidine was administered just before the meal. The rats were provided with food for 30 minutes. The intragastric pH was measured under isoflurane anesthesia, and the GER was measured after harvesting the stomach. In the stress experiment, rats were exposed to 1-hour restraint stress immediately after mosapride administration and subjected to the same process as in the experiment with the non-stressed rats. @*Results@#The famotidine-only and combination groups showed significantly higher gastric pH levels than the control group in non-stressed (P<0.01 and P<0.001, respectively) and stressed (P<0.001 and P<0.001, respectively) rats. The combination group also showed significantly higher intragastric pH levels than the famotidine-only group in non-stressed (P<0.01) and stressed (P<0.05) rats. Additionally, combination groups showed a significantly higher GER than the famotidine-only group in non-stressed (P<0.001) and stressed (P<0.01) rats. @*Conclusions@#The combination of mosapride with famotidine significantly increased intragastric pH compared to famotidine alone in the non-stressed and stressed rats.

Effect of Combination Therapy of Oral Famotidine with Mosapride on Intragastric pH and Gastric Emptying in Rats

Background/Aims@#Studies in healthy humans have reported that the addition of mosapride to acid suppressants resulted in higher intragastric pH than acid suppressant administration alone. We investigated the effect of the addition of mosapride to famotidine on the intragastric pH and gastric emptying rate (GER) in rats. @*Materials and Methods@#Sixty male Wistar rats were used in this study. Experimental groups were divided into control, famotidine-only, mosapride-only, and famotidine with mosapride (combination). The first experiment was performed in non-stressed rats. Mosapride was administered by oral gavage 1 hour before the meal, and famotidine was administered just before the meal. The rats were provided with food for 30 minutes. The intragastric pH was measured under isoflurane anesthesia, and the GER was measured after harvesting the stomach. In the stress experiment, rats were exposed to 1-hour restraint stress immediately after mosapride administration and subjected to the same process as in the experiment with the non-stressed rats. @*Results@#The famotidine-only and combination groups showed significantly higher gastric pH levels than the control group in non-stressed (P<0.01 and P<0.001, respectively) and stressed (P<0.001 and P<0.001, respectively) rats. The combination group also showed significantly higher intragastric pH levels than the famotidine-only group in non-stressed (P<0.01) and stressed (P<0.05) rats. Additionally, combination groups showed a significantly higher GER than the famotidine-only group in non-stressed (P<0.001) and stressed (P<0.01) rats. @*Conclusions@#The combination of mosapride with famotidine significantly increased intragastric pH compared to famotidine alone in the non-stressed and stressed rats.

How to Study the Sex and Gender Effect in Biomedical Research? / 대한소화기학회지

Men and women are different, but this difference has not been well reflected in clinical trials and preclinical studies of biomedical science. Gender medicine, which systematically analyzes research results according to sex and gender, has been emphasized to overcome this problem. On the other hand, researchers still have difficulty in applying gender medicine to their research. To perform rigorous gender medicine, using correct terms, a thorough literature review during research planning, appropriate statistical analysis and reporting, and cautious interpretation of the results are necessary. Applying gender medicine will increase the reproducibility of studies, promote discoveries, expand the study relevance, and ultimately improve patient care in both men and women. Here, this study reviewed the practical issues on applying gender medicine to both preclinical and clinical studies in the field of biomedical science.

Protective Effect of Cilostazol Against Restraint Stress Induced Heart Failure in Post-Myocardial Infarction Rat Model / 전남의대학술지

Cilostazol, a phosphodiesterase III inhibitor, has antiplatelet and vasodilatory effects.It also has pleiotrophic effects including reduction of oxygen free radicals, positive chronotropic effect and inhibition of intracellular Ca2+ associated catecholamine secretion. The study was aimed to examine, in vivo, the effects of cilostazol treatments on myocardial function, myocardial remodeling, and neurohormonal status in myocardial infarction (MI) with restrained stress rat model. Male Sprague Dawley rats, subjected to coronary artery ligation to induce myocardial infarction (MI), received either a standard rat chow alone (control, n=5) or combined with cilostazol (cilostazol, n=5; 5 mg/kg×5 weeks). They were exposed to repeated restraint stress (2 h×2 times/day) for 10 days beginning 1 week after surgery. Left ventricular ejection fraction (LVEF), LV mass by heart weight/body weight ratio and level of tissue brain natriuretic peptide (BNP) expression by immunoblotting were determined. Plasma epinephrine and norepinephrine levels were also measured. Mean LVEF was higher in the cilostazol group than in the control group (66.9±14.3 vs 47.0±17.1, p<0.05) at 5 weeks after MI. However, LV mass and tissue BNP expression were significantly lower in the cilostazol than in the control group (p<0.05). Plasma epinephrine and norepinephrine levels were also lower in the cilostazol group compared with the control (p<0.05). Cilostazol preserves left ventricular systolic function and attenuates stress induced remodeling in postinfarct rats. Its beneficial effects were associated with reduced plasma catecholamine levels during postinfarct remodeling.

The Role of Gut Microbiota and Use of Probiotics in the Treatment of Upper Gastrointestinal Diseases

Gut microbiota have been known to play an essential role in host immunity and metabolism. Dysbiosis is associated with various gastrointestinal (GI) and other diseases such as cancers, metabolic diseases, allergies, and immunological disorders. So far, the role of gut microbiota has been studied mainly in lower GI disease but has recently been reported in upper GI diseases other than Helicobacter pylori infection, including Barrett's esophagus, esophageal carcinoma, gastric cancer, functional dyspepsia, and non-steroidal anti-inflammatory drug-induced small intestinal mucosal injury. Probiotics have some beneficial effect on these diseases, but the effects are strain specific.

Effect of DA-9701 on Feeding Inhibition Induced by Acute Restraint Stress in Rats

BACKGROUND/AIMS: Stress has a role in the pathogenesis of functional dyspepsia (FD) and influences food intake in humans and animals. Prokinetic drugs have been used in FD, and some of these drugs reverse the feeding inhibition (FI) induced by acute restraint stress in rats. We aimed to evaluate the effect of DA-9701 on FI induced by acute restraint in rats. MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into 6 groups: Control (no stress), Stress+vehicle, and Stress+DA-9701 at doses of 1, 3, 10, and 30 mg/kg (n=6~7). DA-9701 or vehicle was administered through gastric gavage 45 minutes before stress. After 60 minutes of stress, pre-weighed chow was given and the weight of remaining food was measured 30 and 60 minutes later. The effect of DA-9701 on FI was compared after pretreatment with WAY100635, a 5HT1A antagonist. RESULTS: The restraint stress group had significantly less food intake than the control group. After feeding, rats given 1 and 3 mg/kg of DA-9701 showed increased food intake at 60 minutes, but this was not statistically significant. Rats given 10 mg/kg of DA-9701 showed significantly increased food intake at 30 minutes and 60 minutes (P < 0.05). Interestingly, rats given 30 mg/kg of DA-9701 showed a significant decrease in food intake, similar to that of the vehicle group. The beneficial effect of 10 mg/kg of DA-9701 on FI was abolished by the pretreatment with WAY100635. CONCLUSIONS: Acute restraint stress reduced food intake in rats and pretreatment with DA-9701 improved stress-induced FI.

Comparison of Changes in the Interstitial Cells of Cajal and Neuronal Nitric Oxide Synthase-positive Neuronal Cells With Aging Between the Ascending and Descending Colon of F344 Rats

BACKGROUND/AIMS: Neuronal degeneration and changes in interstitial cells of Cajal (ICCs) are important mechanisms of age-related constipation. This study aims to compare the distribution of ICCs and neuronal nitric oxide synthase (nNOS) with regard to age-related changes between the ascending colon (AC) and descending colon (DC) in 6-, 31-, and 74-week old and 2-year old male Fischer-344 rats. METHODS: The amount of fecal pellet and the bead expulsion times were measured. Fat proportion in the muscle layer of the colon was analyzed by hematoxylin and eosin staining. Proto-oncogene receptor tyrosine kinase (KIT) and neuronal nitric oxide synthase (nNOS) expression were analyzed with Western blotting and immunohistochemistry. Isovolumetric contractile measurements and electrical field stimulation were used to assess smooth muscle contractility. RESULTS: Colon transit and bead expulsion slowed with senescence. Fat in the muscle layer accumulated with age in the AC, but not in the DC. The proportion of KIT-immunoreactive ICCs in the submucosal and myenteric plexus was higher in the DC than in the AC, and it declined with age, especially in the AC. In contrast, the proportion of NOS-immunoreactive neurons in the myenteric plexus was higher in the AC than in the DC, and both decreased in older rats. Nitric oxide levels declined with age in the DC. Muscle strip experiments showed that the inhibitory response mediated by nitric oxide in the circular direction of the DC was reduced in 2-year old rats. CONCLUSION: The AC and DC differ in their distribution of ICCs and nNOS, and age-related loss of nitrergic neurons more severely affects the DC than the AC.

Neuroimaging and Clinicopathologic Findings of Lymphoplasmacyte-rich Meningioma, Mimicking Malignancy: Case Report

Lymphoplasmacyte-rich meningioma is a rare WHO Grade I subtype of meningioma. The lymphoplasmacyte-rich meningioma does not have typical imaging features of a meningioma so it can mimic intracranial inflammatory condition or brain neoplasm. We report the clinicopathologic features of lymphoplasmacyte-rich meningioma in a 35-year-old woman. She suffered from progressive headache, dizziness and tinnitus over two years. The tumor exhibited atypical neuroimaging features, including obvious peritumoral edema and irregular enhancing components. She underwent total resection and histologic examination revealed a meningioma with numerous plasma cells. Her symptoms have since resolved and there has been no evidence of tumor recurrence after one year of follow-up.

Serum Response Factor Is Essential for Prenatal Gastrointestinal Smooth Muscle Development and Maintenance of Differentiated Phenotype

BACKGROUND/AIMS: Smooth muscle cells (SMCs) characteristically express serum response factor (SRF), which regulates their development. The role of SRF in SMC plasticity in the pathophysiological conditions of gastrointestinal (GI) tract is less characterized. METHODS: We generated SMC-specific Srf knockout mice and characterized the prenatally lethal phenotype using ultrasound biomicroscopy and histological analysis. We used small bowel partial obstruction surgeries and primary cell culture using cell-specific enhanced green fluorescent protein (EGFP) mouse lines to study phenotypic and molecular changes of SMCs by immunofluorescence, Western blotting, and quantitative polymerase chain reaction. Finally we examined SRF change in human rectal prolapse tissue by immunofluorescence. RESULTS: Congenital SMC-specific Srf knockout mice died before birth and displayed severe GI and cardiac defects. Partial obstruction resulted in an overall increase in SRF protein expression. However, individual SMCs appeared to gradually lose SRF in the hypertrophic muscle. Cells expressing low levels of SRF also expressed low levels of platelet-derived growth factor receptor alpha (PDGFRalphalow) and Ki67. SMCs grown in culture recaptured the phenotypic switch from differentiated SMCs to proliferative PDGFRalphalow cells. The immediate and dramatic reduction of Srf and Myh11 mRNA expression confirmed the phenotypic change. Human rectal prolapse tissue also demonstrated significant loss of SRF expression. CONCLUSIONS: SRF expression in SMCs is essential for prenatal development of the GI tract and heart. Following partial obstruction, SMCs down-regulate SRF to transition into proliferative PDGFRalphalow cells that may represent a phenotype responsible for their plasticity. These findings demonstrate that SRF also plays a critical role in the remodeling process following GI injury.

Does Decreased c-KIT Expression in Myenteric Interstitial Cells of Cajal Cause Decreased Spontaneous Contraction in Murine Proximal Colon?

No abstract available.

Clinical Relevance of Serotonin Receptor Splice Variant Distribution in Human Colon

No abstract available.

Regional Differences in Chronic Stress-induced Alterations in Mast Cell and Protease-activated Receptor-2-positive Cell Numbers in the Colon of Ws/Ws Rats

BACKGROUND/AIMS: There have been no reports on the effect of chronic psychological stress on colonic immune cells or the regional differences. We aimed to investigate the effect of chronic psychological stress on the number of mast cells and protease-activated receptor (PAR)-2-positive cells in the rat colonic mucosa. METHODS: Six-week-old and 14-week-old Ws/Ws rats, which lack mast cells after 10 weeks, were used as control and mast cell-deficient groups, respectively. The rats were divided into stress and sham-treated groups. Rats in the stressed group were exposed to water avoidance stress (WAS, 1 hour/day) for 13 days. Fecal pellet output and the number of mast cells and PAR-2-positive cells in colonic mucosa were compared between the WAS and sham groups. RESULTS: In 6-week-old rats, the WAS group showed a significantly higher number of mast cells compared to the sham group. In 14-week-old rats, mast cells were nearly absent in the colonic mucosa. WAS significantly increased PAR-2-positive cells in 14-week-old rats, but not in 6-week-old rats. Indirect estimation of PAR-2-positive mast cells in 6-week-old rats suggested that the majority of increased mast cells following WAS did not express PAR-2. WAS increased mast cells and PAR-2-positive cells mainly in the proximal colon. Fecal pellet output was continuously higher in the WAS group than in the sham group, and the difference was significant for both 6-week-old and 14-week-old rats. CONCLUSIONS: Chronic psychological stress increased the number of mast cells and PAR-2-positive cells in rat colonic mucosa, and these increases were more prominent in the proximal colon.

Effects of Bladder Function by Early Tamsulosin Treatment in a Spinal Cord Injury Rat Model

OBJECTIVE: To investigate the effects of early tamsulosin treatment on changes in bladder characteristics after a spinal cord injury. METHODS: We divided 45 rats into three groups: the control (CON) group, the spinal cord injury (SCI) group, and the SCI+tamsulosin treatment (SCI+TAM) group. Spinal cord transection was performed in the SCI and SCI+TAM groups. Tamsulosin was injected for 7 days in the SCI+TAM group. Intravesical and intra-abdominal catheters were implanted before cord injury. Basal pressure (BP), maximal vesical pressure (MVP), micturition volume (MV), and voiding interval time (VIT) were measured at 7 days after SCI. The bladder was then removed and used for an in vitro organ bath study and Western blot analysis. The percentage changes in contractility from baseline after acetylcholine alone, pretreatment with a muscarinic 2 (M2) receptor blocker (AQ-RA741), and pretreatment with a M3 receptor blocker (4-DAMP) were compared among the groups. Western blot analyses were performed to determine expression levels of pERK1/2 and rho-kinase. RESULTS: In cystometry, MVP, BP, MV, and VIT showed changes in the SCI and SCI+TAM groups versus the CON group (p<0.05). In the organ bath study, acetylcholine-induced contractility in the three groups differed significantly (p<0.05). Additionally, acetylcholine-induced contractility with 4-DAMP pretreatment was reduced significantly in the SCI+TAM group versus the SCI group. In Western blotting, pERK1/2 expression was stronger (p<0.05) and rho-kinase expression was weaker in the SCI+TAM group than the SCI group (p<0.05). CONCLUSION: These results suggest that the bladder contraction due to acetylcholine after SCI can be decreased by tamsulosin in the acute stage and this involves changes in pERK1/2 and rho-kinase.

Seed-borne Brachycladium penicillatum Intercepted under Plant Quarantine Inspection in Korea

A fungus detected from the importing seeds of Papaver rhoeas under plant quarantine inspection in Korea was identified as Brachycladium penicillatum Corda. It differed in morphological characteristics from a similar species, B. papaveris, which was known to form no macroconidiophores and no microsclerotia. Since the first interception in 2006, this fungus has frequently been found from importing seeds of Papaver spp. It was detected from 31 out of 282 seed consignments imported from 2006 to 2011. To prevent its introduction to Korea, the seed consignments infested by B. penicillatum were destroyed or reshipped.

Bowel Dysfunction and Colon Transit Time in Brain-Injured Patients

OBJECTIVE: To report the defecation patterns of brain-injured patients and evaluate the relationship between functional ability and colon transit time (CTT) in stroke patients. METHOD: A total of 55 brain-injured patients were recruited. Patient interviews and medical records review of pattern of brain injury, anatomical site of lesion, bowel habits, constipation score, and Bristol scale were conducted. We divided the patients into constipation (n=29) and non-constipation (n=26) groups according to Rome II criteria for constipation. The CTTs of total and segmental colon were assessed using radio-opaque markers Kolomark(R) and functional ability was evaluated using the functional independence measure (FIM). RESULTS: Constipation scores in constipation and non-constipation groups were 7.32+/-3.63 and 5.04+/-2.46, respectively, and the difference was statistically significant. The CTTs of the total colon in both groups were 46.6+/-18.7 and 32.3+/-23.5 h, respectively. The CTTs of total, right, and left colon were significantly delayed in the constipation group (p<0.05). No significant correlation was found between anatomical location of brain injury and constipation score or total CTT. Only the CTT of the left colon was delayed in the patient group with pontine lesions (p<0.05). CONCLUSION: The constipation group had significantly elevated constipation scores and lower Bristol stool form scale, with prolonged CTTs of total, right, and left colon. In classification by site of brain injury, we did not find significantly different constipation scores, Bristol stool form scale, or CTTs between the groups with pontine and suprapontine injury.

Changes in the Muscarinic Receptors on the Colonic Smooth Muscles of Rats with Spinal Cord Injury

OBJECTIVE: To investigate changes in (1) the colonic response to acetylcholine (Ach), (2) the muscarinic (M) receptors in the colon, and (3) the levels of colonic contraction-related proteins after a spinal cord injury (SCI). METHOD: We divided 16 Sprague-Dawley rats into 2 groups: the control group and the SCI group. A spinal cord transection was performed surgically at the T10 vertebral level. After 1 week, the entire colon was divided into 2 segments, the proximal and distal colon. Each segment was mounted in a longitudinal or circular muscle direction in a 10-ml organ bath. We determined the intergroup differences as percentage changes in contractility after Ach treatment alone, Ach treatment with M2 receptor antagonist (AQ-RA741) pretreatment, and Ach treatment with M3 receptor antagonist (4-DAMP) pretreatment. Western blot analyses were performed to determine the expression level of RhoA, and heat shock protein 27 (HSP27). RESULTS: Compared to the control rats, the SCI rats showed an increased response to Ach along both the directions in the proximal colon (p<0.05). Compared to the control group, in the SCI group, the Ach response was significantly different in the proximal segment under AQ-RA741 pretreatment (p<0.05) and in the distal segment under 4-DAMP pretreatment (p<0.05). Findings of the western blot analyses showed a significant decrease in the level of protein gene product 9.5 in the proximal and distal colon and a significant increase in the level of RhoA and HSP27 in the proximal colon of the SCI rats. CONCLUSION: Our results suggest that changes in colonic contractility after SCI are partly attributable to changes in the M receptor subtypes.

Change of Tetrodotoxin Sensitive Inhibitory Neural System of the Colon in Spinal Cord Injured Rats

OBJECTIVE: To investigate the effect of spinal cord injury (SCI) on contractions of whole colonic preparation isolated from rats under the inhibition of nitrergic inhibitory neural system using tetrodotoxin (TTX). METHOD: Twenty Sprague-Dawley rats were used. A complete spinal cord transection was performed surgically at the T10 cord level in spinal cord injured group. After 1 week of operation, sensory and motor functions were assessed and colon was removed under anesthesia for in vitro motility study. Whole colon was divided into four segments: proximal, two mid colon and distal colon. Each segment of colon was mounted with longitudinal direction in a 10 ml organ bath. After 1 hour of equilibration, frequency, area under the curve of spontaneous contraction and the response to acetylcholine (Ach), KCl and TTX were measured in each segment. Also the responses to Ach and KCl response under TTX pretreatment were measured. RESULTS: Enhanced contractile response to KCl solution (40 mM), TTX (1 micrometer) and Ach (10(-6) M) was observed in both group. There was no statistical difference in spontaneous, Ach and KCl induced contraction between control and SCI rats, but TTX induced contraction was decreased in SCI group than control group (p<0.05). In addtion, the Ach and KCl responses under the TTX pretreatment were significantly decreased in SCI group than control group (p<0.05). CONCLUSION: These results suggest that the change of colonic contractility after the SCI is caused by at least partly from the change of TTX related inhibitory neural system.

Chronic Administration of Monosodium Glutamate under Chronic Variable Stress Impaired Hypothalamic-Pituitary-Adrenal Axis Function in Rats

The hypothalamic-pituitary-adrenal (HPA) axis is the primary endocrine system to respond to stress. The HPA axis may be affected by increased level of corticotrophin-releasing factors under chronic stress and by chronic administration of monosodium glutamate (MSG). The purpose of this study was to investigate whether chronic MSG administration aggravates chronic variable stress (CVS)-induced behavioral and hormonal changes. Twenty-four adult male Sprague-Dawley rats, weighing 200~220 g, were divided into 4 groups as follows: water administration (CON), MSG (3 g/kg) administration (MSG), CVS, and CVS with MSG (3 g/kg) administration (CVS+MSG). In addition, for the purpose of comparing the effect on plasma corticosterone levels between chronic stress and daily care or acute stress, 2 groups were added at the end of the experiment; the 2 new groups were as follows: naive mice (n=7) and mice exposed to restraint stress for 2 h just before decapitation (A-Str, n=7). In an open field test performed after the experiment, the CVS+MSG group significant decrease in activity. The increase in relative adrenal weights in the CVS and CVS+MSG group was significantly greater than those in the CON and/or MSG groups. In spite of the increase in the relative adrenal weight, there was a significant decrease in the plasma corticosterone levels in the CVS+MSG group as compared to all other groups, except the naive group. These results suggest that impaired HPA axis function as well as the decrease in the behavioral activity in adult rats can be induced by chronic MSG administration under CVS rather than CVS alone.

Phosphorylation of Extracellular Signal-Regulated Kinase1/2 and Caldesmon in Rat Colon by Electrical Stimulation to Sacral Plexus Following Spinal Cord Injury

OBJECTIVE: To find out whether electrical stimulation affects intracellular signaling mechanisms that link the biochemical and mechanical events of smooth muscle contraction. METHOD: A total of 31 adult Sprague-Dawley female rats were divided into 3 groups: control group, spinal cord injury (SCI) only group, and spinal cord injury with electrical stimulation (SCI+ES) group. Complete spinal cord transection was performed surgically at T10 cord level. The electrode for electrical stimulation was implanted into sacral spinal cord region (S2-4). Electrical stimulation was applied 4 hours per day from the day of operation. RESULTS: In SCI+ES group, the weights of fecal pellet were significantly higher from the 3rd day of post-operation to the 6th day than the SCI only group. The numbers of pERK 1/2 immunoreactive cells significantly increased in all colon segments of the SCI+ES group but had decreased in the SCI only group. Western blot showed the stronger bands of phosphorylated ERK1/2 in all colon segments and also phosphorylated caldesmon in mid or distal colon segments in the SCI+ES group. CONCLUSION: These results suggest that electrical stimulation to sacral plexus region activate phosphorylation of ERK1/2 and caldesmon which leads to improvement of bowel function by promotion of secretion or motility in the colon.

c-fos mRNA Expression in the Vestibular System following Hypergravity Stimulation in Rats

Altered environmental gravity, including both hypo- and hypergravity, may result in space adaptation syndrome. To explore the characteristics of this adaptive plasticity, the expression of immediate early gene c-fos mRNA in the vestibular related tissues following an exposure to hypergravity stimulus was determined in rats. The animals were subjected to a force of 2 g (twice earth's gravity) for 1, 3, or 12 h, and were examined poststimulus at 0, 2, 6, 12, and 24 h. RT-PCR (reverse transcription polymerase chain reaction) and real-time quantitative RT-PCR were adopted to analyze temporal changes in the expression of c-fos mRNA. The hypergravity stimulus increased the expression of c-fos mRNA in the vestibular ganglion, medial vestibular nucleus, inferior vestibular nucleus, hippocampus, cerebellum, and cortex. The peak expression occurred at 0 h poststimulation in animals stimulated with hypergravity for 1 h, and at 6 h poststimulus in those stimulated for 3 h. In contrast, those stimulated for 12 h exhibited dual peaks at 0 and 12 h poststimulus. Bilateral labyrinthectomy markedly attenuated the degree of c-fos mRNA expression. Glutamate receptor antagonist also dramatically attenuated the degree of c-fos mRNA expression. These results indicate that expression of c-fos mRNA in response to hypergravity occurs in the vestibular related tissues of the central nervous system, in which peripheral vestibular receptors and glutamate receptors play an important role. The temporal pattern of c-fos mRNA expression depended on the duration of the hypergravity stimulus.