Identification and molecular study on the interaction of Schisandrin C with human 5-HT3A receptor.

Schisandrin C (Sch C) is one of the main components of Schisandra chinensis (Schisandra). Since the olden times, Schisandra has been used as a traditional herbal medicine in Asia. Recent studies have shown that Schisandra is effective against irritable bowel syndrome (IBS) in an animal model and affects IBS through the 5-HT3A pathway in the IBS rat model. However, there lacks fundamental research on the interaction of specific components of Schisandra with the 5-HT3A receptor for the treatment of IBS. We hypothesized that a component of Schisandra binds to the 5-HT3A receptor and identified Sch C via a screening work using two electrode-voltage clamps (TEVC). Thus, we aimed to elucidate the neuropharmacological actions between Sch C and the 5-HT3A receptor at molecular and cellular levels. Co-treatment of Sch C with 5-HT inhibited I5-HT in a reversible, concentrate-dependent, like-competition, and voltage-independent manner, and IC50 values of Sch C. Besides, the main binding positions of Sch C were identified through 3D modeling and point mutation were V225A and V288Y on 5-HT3A receptor. Thus, we suggest the potential of Sch C in treating IBS in a manner that suppresses excessive neuronal serotonin signaling in the synapse of sensory neurons and enterochromaffin (EC) cells. In conclusion, the results demonstrate the mechanism of interaction between Sch C and 5-HT3A receptor and reveal Sch C as a novel antagonist.

Modified Liu-Jun-Zi decoction alleviates visceral hypersensitivity in functional dyspepsia by regulating EC cell-5HT3r signaling in duodenum.

ETHNOPHARMACOLOGICAL RELEVANCE: Modified Liu-Jun-Zi (MLJZ) is derived from one of the most famous traditional Chinese prescription Liu-Jun-Zi. It exhibits therapeutic effects in functional dyspepsia (FD), but the underlying mechanisms remain not well understood. Enterochromaffin (EC) cells contribute to the pathogeneses of visceral hypersensitivity in functional gastrointestinal disorders. But whether and how EC cells in duodenum participate in the mechanism of FD remain unsettled. AIM OF THE STUDY: To detect the crucial factors related to EC cells, and to evaluate the therapeutic effect of MLJZ and to determine whether MLJZ relieves visceral hypersensitivity in FD by regulating EC cell-5-hydroxytryptamine 3 receptor (5HT3r) signaling. MATERIALS AND METHODS: FD rats were established by iodoacetamide gavage combined with tail clamping method. The verification of FD model and the evaluation of the therapeutic effect of MLJZ was taken place by hematoxylin-eosin (HE) staining and visceral sensitivity measurement. The expression of EC cells and 5-hydroxytryptamine (5HT) in duodenum was detected by Immunohistochemistry (IHC) staining and enzyme-linked immunosorbent assay (ELISA). IHC staining and quantitative polymerase chain reaction (qPCR) were applied to measure the expression of tryptophan hydroxylase-1 (TPH1), paired box gene 4 (PAX4), transient receptor potential A1 (TRPA1), transient receptor potential C4 (TRPC4) and 5HT3r. Duodenum sections were stained by double immunofluorescence (IF) to study the synthesis of 5HT in EC cells. RESULTS: The gastric sensitivity increased in FD rats while MLJZ decoction significantly attenuated visceral hypersensitivity. The duodenum of FD rats displayed increased expressions of EC cells, 5HT, TPH1, PAX4 and 5HT3r. And the overexpression was reduced in response to MLJZ decoction treatment. CONCLUSIONS: EC cell-5HT3r signaling pathway is abnormally active in FD with visceral hypersensitivity. And MLJZ decoction can alleviates visceral hypersensitivity in FD by regulating EC cell-5HT3r signaling in duodenum.

Quercetin Attenuates Visceral Hypersensitivity and 5-Hydroxytryptamine Availability in Postinflammatory Irritable Bowel Syndrome Rats: Role of Enterochromaffin Cells in the Colon.

Intestinal enterochromaffin (EC) cell hyperplasia and increased 5-hydroxytryptamine (5-HT) availability play key roles in the pathogenesis of abdominal hypersensitivity of irritable bowel syndrome (IBS). This study aims to study the effect of quercetin on visceral pain and 5-HT availability in postinflammatory IBS (PI-IBS) rats. PI-IBS model rats were administered quercetin by gavage at doses of 5, 10, and 20 mg/kg for 14 days. Compared with normal rats, the visceral pain threshold of PI-IBS rats was markedly decreased and the abdominal motor response to colon distension was markedly increased. The EC cell count and 5-HT level, as well as tryptophan hydroxylase (TPH) protein, were all significantly elevated in PI-IBS rats, while the 5-HT reuptake transporter (serotonin transporter) was reduced. Genes that are responsible for enteroendocrine cell differentiation, that is, Ngn3 and pdx1, were significantly increased in the PI-IBS group. Quercetin treatment markedly elevated the pain threshold pressure and decreased the visceral motor response of PI-IBS animals; and EC cell density and 5-HT level, as well as TPH expression, in the PI-IBS group were all reduced by quercetin. Quercetin treatment also significantly reduced colonic expression of Ngn3 and pdx1 of PI-IBS. Findings from the present study indicated that the analgesic effect of quercetin on PI-IBS may result from reduction of 5-HT availability in the colon, and the regulatory role of quercetin in endocrine progenitors may contribute to reduced EC cells.

Possible anti-inflammatory role of Zingiberis processum rhizoma, one component of the Kampo formula daikenchuto, against neutrophil infiltration through muscarinic acetylcholine receptor activation.

Zingiberis processum rhizoma (ZPR) is a major active component of daikenchuto (DKT), which induces anti-inflammatory action by inhibiting macrophage infiltration. However, it is unclear whether ZPR is related to DKT-induced anti-inflammatory action via a reduction of neutrophil infiltration against postoperative ileus (POI). In this study, we orally administered individual herbal components of DKT to mice four times before and after intestinal manipulation (IM). The anti-inflammatory action of each crude drug was evaluated by histochemical analysis of relevant molecules. The results showed that treatment with all herbal components of DKT significantly inhibits neutrophil infiltration. This inhibition of neutrophil infiltration by ZPR was significantly reduced in 5-hydroxytryptamine receptor 4 (5-HT4R) knockout (KO) mice but not in alpha-7 nicotinic acetylcholine receptor (α7nAChR) KO mice. Also, transient receptor potential ankyrin 1 (TRPA1) and muscarinic acetylcholine receptor (mAChR) antagonists partly and significantly inhibited the amelioration of neutrophil infiltration by ZPR. Therefore, DKT-induced anti-inflammatory action, mediated by inhibition of neutrophil infiltration in POI, depends, in part, on the effects of ZPR. ZPR activates TRPA1 channels, possibly in enterochromaffin (EC) cells, to release 5-HT. This 5-HT stimulates 5-HT4R in the myenteric plexus neurons to release acetylcholine, which, in turn, activates mAChR to inhibit inflammation in POI.

Nutrient-induced glucagon like peptide-1 release is modulated by serotonin.

Glucagon like peptide-1 (GLP-1) and serotonin are both involved in food intake regulation. GLP-1 release is stimulated upon nutrient interaction with G-protein coupled receptors by enteroendocrine cells (EEC), whereas serotonin is released from enterochromaffin cells (ECC). The central hypothesis for the current study was that nutrient-induced GLP-1 release from EECs is modulated by serotonin through a process involving serotonin receptor interaction. This was studied by assessing the effects of serotonin reuptake inhibition by fluoxetine on nutrient-induced GLP-1, PYY and CCK release from isolated pig intestinal segments. Next, serotonin-induced GLP-1 release was studied in enteroendocrine STC-1 cells, where effects of serotonin receptor inhibition were studied using specific and non-specific antagonists. Casein (1% w/v), safflower oil (3.35% w/v), sucrose (50mM) and rebaudioside A (12.5mM) stimulated GLP-1 release from intestinal segments, whereas casein only stimulated PYY and CCK release. Combining nutrients with fluoxetine further increased nutrient-induced GLP-1, PYY and CCK release. Serotonin release from intestinal tissue segments was stimulated by casein and safflower oil while sucrose and rebaudioside A had no effect. The combination with fluoxetine (0.155µM) further enhanced casein and safflower oil induced-serotonin release. Exposure of ileal tissue segments to serotonin (30µM) stimulated GLP-1 release whereas it did not induce PYY and CCK release. Serotonin (30 and 100µM) also stimulated GLP-1 release from STC-1 cells, which was inhibited by the non-specific 5HT receptor antagonist asenapine (1 and 10µM). These data suggest that nutrient-induced GLP-1 release is modulated by serotonin through a receptor mediated process.

Oridonin Alleviates Visceral Hyperalgesia in a Rat Model of Postinflammatory Irritable Bowel Syndrome: Role of Colonic Enterochromaffin Cell and Serotonin Availability.

The aim of this present study was to investigate the effect of oridonin on visceral hyperalgesia and colonic serotonin availability in a rat model of trinitrobenzenesulfonic acid-induced postinflammatory irritable bowel syndrome (PI-IBS). Rats were randomly divided into five groups: normal control, PI-IBS model, PI-IBS+low-dose oridonin (5 mg/kg), PI-IBS+median-dose oridonin (10 mg/kg), and PI-IBS+high-dose oridonin (20 mg/kg). Rats in control and model groups were orally administered with water by gavage, whereas rats in oridonin-treated groups were orally administered with different dosages of oridonin, and drugs were given for 14 consecutive days. Compared with the control group, the pain threshold pressure was significantly reduced in PI-IBS rats. The colonic enterochromaffin (EC) cell number, serotonin content, and the protein expression of tryptophan hydroxylase (TPH) were markedly increased and the protein expression of serotonin reuptake transporter was significantly decreased in PI-IBS rats. The spleen index in PI-IBS rats was decreased, and the levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-4, and IL-13 in the colon of PI-IBS rats were also markedly decreased. Oridonin treatment dose dependently increased pain threshold pressure, and markedly decreased colon EC cell numbers, TPH expression, and serotonin content in PI-IBS rats. Oridonin treatment also significantly increased the spleen index as well as the levels of TNF-α, IFN-γ, IL-4, and IL-13 in the colon of PI-IBS rats. Results of this study demonstrate that the analgesic effect of oridonin in PI-IBS rats is associated with reduced colonic EC cell hyperplasia and 5-HT availability, the regulatory effect of oridonin on colonic cytokine production may be correlated with its effect on colonic EC cell number.

Gastric mucosal protection by aegle marmelos against gastric mucosal damage: role of enterochromaffin cell and serotonin.

BACKGROUND/AIMS: Serotonin (5-hydroxytryptamine; 5-HT) released from enterochromaffin (EC) cells in gastric mucosa inhibits gastric acidity by increasing the gastric mucus secretion. In the present study, we evaluated the effect of aqueous extract of Aegle marmelos (AM) ripe fruit pulp (250 mg/kg body weight) on mean ulcer index (MUI), EC cells, 5-HT content, and adherent mucosal thickness of ulcerated gastric tissue in adult albino rats. MATERIAL AND METHODS: Ulceration was induced by using aspirin (500 mg/kg, p.o.), cerebellar nodular lesion and applying cold-restraint stress. RESULTS: In all cases increased MUI in gastric tissue along with decreased EC cell count was observed with concomitant decrease of 5-HT content and adherent mucosal thickness (P < 0.05). Pretreatment with AM for 14 days decreased MUI, increased EC cell count, and 5-HT content as well as adherent mucosal thickness in all ulcerated group (P < 0.05). CONCLUSION: AM produces gastric mucosal protection mediated by increased EC cell count and 5-HT levels.

Anticolitis activity of Chinese herbal formula yupingfeng powder via regulating colonic enterochromaffin cells and serotonin.

OBJECTIVE: To investigate whether traditional Chinese herbal formula Yupingfeng (YPF) powder has an anti-inflammatory effect on colonic inflammation, and to explore the mechanism involved. MATERIALS AND METHODS: YPF powder was orally administrated to trinitrobenzene sulfonic acid (TNBS)-induced colitis mice at the dose of 3, 6, and 12 g/kg/d for 7 consecutive days. Body weight, stool consistency, histopathological score, and myeloperoxidase (MPO) activity were tested to evaluate the effect of YPF powder on colonic inflammation while colonic enterochromaffin (EC) cell density and serotonin 5-hydroxytryptamine (5-HT) content were investigated to identify the effect of YPF powder on colonic 5-HT availability. RESULTS: The results showed that the body weight of colitis mice was markedly decreased by 10, 12, 14, and 17% at 1, 3, 5, and 7 days (P < 0.05), whereas stool consistency score (3.6 vs. 0.4, P < 0.05), histopathological score (3.6 vs. 0.3, P < 0.05), and MPO activity (2.7 vs. 0.1, P < 0.05) in colitis mice were significantly increased compared to that of the normal mice; YPF powder treatment dose-dependently increased the body weight (7-13% increase) and decreased the stool consistency score (0.4-1.4 decrease), histopathological score (0.2-0.7 decrease), and MPO activity (0.1-0.9 decrease) in colitis mice. Colonic EC cell density (70% increase) and 5-HT content (40% increase) were markedly increased in colitis mice (P < 0.05), YPF powder treatment dose-dependently reduced EC cell density (20-50% decrease), and 5-HT content (5-27% decrease) in colitis mice. CONCLUSION: The findings demonstrate that the anti-inflammatory effect of YPF powder on TNBS - induced colitis may be mediated via reducing EC cell hyperplasia and 5-HT content. The important role of YPF powder in regulating colonic EC cell number and 5-HT content may provide an alternative therapy for colonic inflammation.

Moringa oleifera induced potentiation of serotonin release by 5-HT(3) receptors in experimental ulcer model.

ETHNOPHARMACOLOGICAL RELEVANCE: moringa oleifera (Moringaceae), a perennial plant is widely cultivated throughout the world. Extensive pharmacological studies revealed its promising role in modulation of various disorders like antispasmodic, diuretic, abortifacient, antimicrobial antibacterial, antitubercular, antiviral, antifertility, depressant, anti-inflammatory and anticancer property which promoted us to conduct the study to elucidate its role on experimental gastric ulceration. AIM OF THE STUDY: the aim of the present study was to assess the efficacy of its aqueous leaf extract on protection of gastric ulceration and characterize the possible modulatory mechanism underlying the phenomenon. MATERIALS AND METHODS: adult Holtzman strain albino rats (weight 150-200 g) of either sex were used for the study. Ulceration was induced using aspirin (500 mg/kg body weight) and using Moringa oleifera (MO), a herbal formulation, the modulatory mechanism has been studied and compared with a commonly used antagonist of 5-HT(3) receptors, ondansetron by assessing parameters like mean ulcer index, 5-HT content, EC cell count and mucosal thickness. RESULTS: the results of our study suggest that MO protects ulcer formation by modulating 5-HT secretion through EC cell via 5-HT(3) receptors in gastrointestinal tract. INTERPRETATION AND CONCLUSION: MO showed maximum protective activity at a dose of 300 mg/kg body weight against above-mentioned experimental rat ulcer model by modulating 5-HT secretion through EC cell via 5-HT(3) receptors in gastrointestinal tract which has given a glimpse of a therapeutic approach for gastric ulcer management, which may be beneficially used in contrast to the classical antacid, antihistamine or surgical treatment. Further investigations and proper screening regarding various phytochemicals, alkaloids present within MO leaf will help to formulate effective herbal preparation that will be used to combat gastrointestinal disorders in future.

Simultaneous measurement of serotonin and melatonin from the intestine of old mice: the effects of daily melatonin supplementation.

Ageing is associated with important changes in gastrointestinal function and in the levels of intestinal hormones secreted. Enterochromaffin (EC) cells containing serotonin (5-HT) and melatonin may play a major role in maintaining gut function during ageing. Our aim was to characterise the mucosal availability of 5-HT and melatonin in the ileum and colon of a mouse model of ageing. Female young mice (2-5 month; n = 6), aged mice (22-24 months; n = 6) and aged mice treated with melatonin (n = 6; 10 mg/kg/day) were examined. Electrochemical methods were used to measure 5-HT and melatonin concentrations near the mucosal surface of ileum and distal colon. Amperometry studies showed that steady state levels of 5-HT from ileum and colon were decreased in aged mice treated with melatonin when compared to aged mice, while compression-evoked 5-HT release was unchanged. Differential pulse voltammetry studies showed that young mice had concentrations of 5-HT of 4.8 +/- 0.8 mum in the ileum and 4.9 +/- 1.0 mum in the colon. Concentrations of melatonin were 5.7 +/- 1.4 mum in the ileum and 5.6 +/- 1.9 mum in the colon. Compared to young mice, the levels of 5-HT and melatonin were increased in aged mice (combined ileum and colon: 5-HT = 130% and melatonin = 126% of young mice) and decreased in melatonin-treated mice (5-HT = 94% and melatonin = 82%). In conclusion, our data show that the availability of gut 5-HT and melatonin is increased in aged mice and melatonin treatment suppresses natural gastrointestinal production of 5-HT and melatonin in the aged mouse intestine.

Analgesic effects of JCM-16021 on neonatal maternal separation-induced visceral pain in rats.

AIM: To investigate the pharmacological effect of JCM-16021, a Chinese herbal formula, and its underlying mechanisms. METHODS: JCM-16021 is composed of seven herbal plant materials. All raw materials of the formula were examined according to the quality control criteria listed in the Chinese Pharmacopeia (2005). In a neonatal maternal separation (NMS) model, male Sprague-Dawley rats were submitted to daily maternal separation from postnatal day 2 to day 14, or no specific handling (NH). Starting from postnatal day 60, rats were administered JCM-16021 (2, 4, 8 g/kg per day) orally twice a day for 28 d. Pain threshold pressure and electromyographic activities of external oblique muscles in response to colorectal distention recorded with a Power Lab System (AD Instruments International), were tested as pain indices. Changes in serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations in the colon of rats were analyzed; the enterochromaffin cell numbers and serotonin transporter in the colon of rats were also evaluated with an immunohistochemistry method. RESULTS: NMS treatment significantly reduced pain threshold pressure (37.4 +/- 1.4 mmHg), as compared to that of NH rats (57.7 +/- 1.9 mmHg, P < 0.05). After JCM-16021 treatment, the pain threshold pressure significantly increased when compared to that before treatment (34.2 +/- 0.9 mmHg vs 52.8 +/- 2.3 mmHg in the high dose group, 40.2 +/- 1.6 mmHg vs 46.5 +/- 1.3 mmHg in the middle dose group, and 39.3 +/- 0.7 mmHg vs 46.5 +/- 1.6 mmHg in the low dose group, P < 0.05). Also JCM-16021 significantly and dose-dependently decreased electromyographic activity to the graded colorectal distension (CRD), (the mean DeltaAUC values were: 0.17 +/- 0.03, 0.53 +/- 0.15, 1.06 +/- 0.18, 1.22 +/- 0.24 in the high dose group; 0.23 +/- 0.04, 0.68 +/- 0.17, 1.27 +/- 0.26, 1.8 +/- 0.3 in the middle dose group; and 0.29 +/- 0.06, 0.8 +/- 0.16, 1.53 +/- 0.24, 2.1 +/- 0.21 in the low dose group for the pressures 20, 40, 60, 80 mmHg), as compared to the NMS vehicle group. The mean DeltaAUC values were: 0.57 +/- 0.12, 1.33 +/- 0.18, 2.57 +/- 0.37, 3.08 +/- 0.37 for the pressures 20, 40, 60, 80 mmHg (P < 0.05). JCM-16021 treatment significantly reduced the 5-HT concentrations (from high, middle and low dosage groups: 60.25 +/- 5.98 ng/100 mg, 60.32 +/- 4.22 ng/100 mg, 73.31 +/- 7.65 ng/100 mg), as compared to the NMS vehicle groups (93.11 +/- 9.85 ng/100 mg, P < 0.05); and increased the 5-HIAA concentrations (after treatment, from high, middle and low dosage groups: 54.24 +/- 3.27 ng/100 mg, 50.34 +/- 1.26 ng/100 mg, 51.37 +/- 2.13 ng/100 mg) when compared to that in the NMS vehicle group (51.75 +/- 1.98 ng/100 mg, P < 0.05); but did not change the enterochromaffin cell numbers in the colon of rats. In addition, NMS rats had higher SERT expression (n = 10) than NH rats (n = 8, P < 0.05). JCM-16021 treatment significantly decreased SERT expression when compared to the NMS group (P < 0.01-0.001). CONCLUSION: JCM-16021 can attenuate visceral hypersensitivity, and this analgesic effect may be mediated through the serotonin signaling pathway in the colon of rats.

Changes in gastric ECL cells and parietal cells after long-term administration of high-dose omeprazole to patients with Barrett's esophagus.

PURPOSE: Long-term administration of PPI causes hyperplastic changes of the gastric parietal cells; however, the detailed mechanism remains to be clarified. We administered high-dose omeprazole to patients with Barrett's esophagus for 2 years, and investigated changes in gastric ECL (Enterochromaffin-like) cells using endoscopic biopsy specimens to clarify the etiology of hyperplasia of the parietal cells. METHODS: The subjects were 69 patients who were diagnosed as having Barrett's esophagus (39 males, 30 females). We established two groups, an omeprazole-treated group and a ranitidine-treated group. Upper digestive tract endoscopy was performed before administration, and 12 and 24 months after the start of administration. Biopsy was performed in the greater curvature of the gastric body. The ECL/parietal cell counts and the grade of hyperplasia of the gastric mucosa were determined under a microscope. In addition, the fasting serum gastrin level was measured, and statistical analysis was performed. RESULTS: In the omeprazole-treated group, the ECL cell count was markedly increased 12 months after the start of administration, but was lower than the pretreatment value 24 months after the start of administration. The parietal and ECL cell counts significantly increased. Furthermore, there were no changes in mucosa thickness. The fasting serum gastrin level significantly increased. In the ranitidine-treated group, there was no increase in the ECL cell count, and the parietal cell count was decreased. There was no significant increase in mucosa thickness. The fasting serum gastrin level increased, although the rate of increase was markedly smaller than that in the omeprazole-treated group. CONCLUSION: Not the direct pharmacological actions of PPI but hypergastrinemia-associated secondary changes may be etiologically involved in hyperplasia of the parietal cells related to long-term administration of PPI.

The somatostatin receptor subtype on rat enterochromaffinlike cells.

BACKGROUND/AIMS: Gastric enterochromaffinlike (ECL) cells play an important role in peripheral regulation of acid secretion. This study investigated the somatostatin receptor subtype on ECL cells. METHODS: ECL cells were isolated from rat fundic mucosa to a purity of 90%-95% by combining enzymatic digestion, elutriation, density gradient centrifugation, and culture. RESULTS: Polymerase chain reaction performed with templates from an ECL cell complementary DNA library and primers specific to each of the five known somatostatin receptor subtypes showed that the somatostatin receptor type 2 was significantly enriched in ECL complementary DNA. Single cell videoimaging of highly purified ECL cells in culture showed that only the somatostatin receptor type 2 selective agonist, DC 32-87, inhibited the gastrin-induced calcium signal at 10(-11) mol/L. The type 3 and type 4 selective agonists, DC 25-12 and DC 32-92, and also somatostatin 14 required 100-1000 times higher concentrations (10(-8) mol/L). The somatostatin receptor type 2 analogue also inhibited gastrin-stimulated histamine release with a 50% inhibitory concentration (IC50) value of 2 x 10(-12) mol/L, whereas somatostatin 14 and the type 3 and 4 analogues showed IC50 values of 1 to 5 x 10(-9) mol/L. CONCLUSIONS: The predominant somatostatin receptors on rat gastric ECL cells are of the somatostatin receptor 2 subtype; they inhibit histamine secretion by interfering with the gastrin-induced calcium signal.

Pharmacologic characterization of opioid peptide release from chromaffin cell transplants using a brain slice superfusion method.

A simple chamber and an inexpensive superfusion system for studying mammalian brain slices containing neural transplants is described. With this method, rat brain slices containing bovine chromaffin cell transplants can be maintained for several hours, allowing for the determination of neurochemical characteristics and pharmacologic responsiveness of the grafted cells. Using this technique, basal and nicotine-stimulated release of metenkephalin from rat periaqueductal gray slices containing bovine chromaffin cell transplants were measured. Results showed that met-enkephalin release can be increased by nicotinic stimulation in slices containing chromaffin cell, but not control implants, for at least 8 weeks postimplantation. Furthermore, this response was dose-related. These results are in good agreement with previous behavioral studies and provide corroborative evidence for the mechanism of pain reduction by the release of opioid peptides from chromaffin cell transplants in the periaqueductal gray. This study demonstrates that neurochemical and pharmacologic analyses of neural transplants using a superfused brain slice method can be a complementary approach in determining the underlying mechanisms of neural transplants in the central nervous system.

[Immunohistochemical study on the enteroendocrine cells of the small intestine in experimental spleen deficiency syndrome in rats].

50 adult Wistar male rats were used and divided into 4 groups, i.e. normal control group, experimental Spleen Deficiency group induced by rhubarb, spontaneous recovery group and therapeutic group treated with Chinese recipe (Si Jun Zi decoction). All the animals of the 4 groups were killed simultaneously, and the jejunum and ileum were removed and processed for demonstration of gastrin cells and 5-HT cells according to immunohistochemical PAP technique. In addition, HE stained samples were prepared. The immunoreactivities of the two types of enteroendocrine cells were observed and semiquantitative estimation were performed under light microscopy. In addition, the immunoreactivities of 5-HT cells in normal control and experimental Spleen Deficiency group were measured by microspectrocytophotometer (MPV 2, Leitz). All the data were treated statistically. This study revealed that there were no obvious histological changes in the mucosa among the 4 groups. In the jejunum, the percentage of gastrin cells(+) in experimental Spleen Deficiency group was more than that of the normal control group, while the percentage of gastrin cells( ) was less than that of the normal control group. As compared with spontaneous recovery group, it showed contrary to the above result in the therapeutic group. No gastrin cells were found in the ileum in all the 4 groups. the percentage of 5-HT cells did not show significant changes in the jejunum and ileum among the 4 groups. But immuno-reactivity in the 5-HT cell was less than that of the normal control group in the jejunum of the Spleen Deficiency group.(ABSTRACT TRUNCATED AT 250 WORDS)

Unilateral vagal denervation suppresses omeprazole-induced trophic effects on the denervated side of the rat stomach.

In several experimental animals treatment with large doses of the proton pump inhibitor omeprazole leads to hypergastrinemia and with time to trophic effects in the acid-producing part of the stomach, most notably an increased density of the histamine-producing enterochromaffin-like (ECL) cells. The trophic effects are thought to reflect the increase in circulating gastrin. In the present study unilateral vagal denervation in the rat partly suppressed the tropic effects seen in the denervated side of the stomach but not those in the intact side after treatment with omeprazole for 10 weeks. Unilateral vagal denervation significantly reduced the proliferative stimulus of omeprazole on the ECL cells in the denervated part of the stomach. Thus, an intact vagal innervation appears to be essential for the capacity of the oxyntic mucosa, including the ECL cells, to respond to elevations in serum gastrin. We suggest that gastrin and the vagus interact to maintain trophic control of the oxyntic glands.