Role of taurine on acid secretion in the rat stomach.

BACKGROUND: Taurine has chemical structure similar to an inhibitory neurotransmitter, γ-aminobutyric acid (GABA). Previous studies on GABA in the stomach suggest GABAergic neuron is involved in acid secretion, but the effects of taurine are poor understood. METHODS: The effects of taurine on acid secretion, signal transduction, and localization of taurinergic neurons were determined in the rat stomach using everted whole stomach, RIA kit and immunohistochemical methods. RESULTS: We used antibodies against taurine-synthesizing enzyme, cysteine sulfuric acid decarboxylase (CSAD), and taurine. CSAD- and taurine-positive cells were found in the muscle and mucosal layers. Distributions of CSAD- and taurine-positive cells in both mucosal and muscle layers were heterogeneous in the stomach. Taurine at 10-9~10-4 M induced acid secretion, and the maximum secretion was at 10-5 M, 1.6-fold higher than the spontaneous secretion. Taurine-induced acid secretion was completely inhibited by bicuculline and atropine but not by cimetidine, proglumide, or strychnine. Atropine and tetrodotoxin (TTX) completely inhibited the acid secretion induced by low concentrations of taurine and partially inhibited induced by high concentrations. Verapamil, a calcium blocker agent, inhibited acid output elicited by taurine. We assumed all Ca2+ channels involved in the response to these secretagogues were equally affected by verapamil. Intracellular cAMP (adenosine 3', 5'-monophosphate) in the stomach significantly increased with taurine treatment in a dose-dependent manner. High correlation (r=0.859, p < 0.001) of taurine concentrations with cAMP was observed. CONCLUSIONS: Our results demonstrated for the first time in taurine-induced acid secretion due to increase intracellular calcium may act through the A type of GABA receptors, which are mainly located on cholinergic neurons though cAMP pathway and partially on nonneuronal cells in the rat stomach.

Ghrelin improves LPS-induced gastrointestinal motility disturbances: roles of NO and prostaglandin E2.

Ghrelin, an important orexigenic peptide, exerts gastroprokinetic and anti-inflammatory effects. We investigated the role of ghrelin in LPS-induced gastrointestinal (GI) motility disturbances through NO and prostaglandin E2 pathways in mice. Ghrelin-containing cells and its receptor, growth hormone secretagogue receptor 1 (GHSR-1), were localized in the stomach and duodenum using an immunohistochemical method. The distribution of ghrelin-containing cells or GHSR-1 immunoreactivity in both the mucosal and the muscle layers was heterogeneous within both tissues. The i.p. administration of ghrelin (1-20 microg/kg) had no effect on gastric emptying but markedly increased the GI transit (GIT) in normal mice. LPS (20 mg/kg i.p.)-treated mice showed significant decreases in the gastric emptying and GIT. Ghrelin attenuated the LPS-induced delay in gastric emptying and GIT. We also performed immunohistochemical experiments on both tissues. Immunohistochemistry showed the presence of iNOS and cyclooxygenase 2 in both tissues of LPS-treated mice. Treatment of LPS-exposed mice with ghrelin (20 microg/kg) diminished the presence of iNOS but not cyclooxygenase 2 in both tissues. The effect of ghrelin on regulating LPS-induced GI motility disturbance was further found to be associated with a reduction in iNOS expression in the GI tract and plasma NO overproduction rather than regulation of neural or endothelial NO synthase expression in the GI tissue. In addition, ghrelin was found to elevate prostaglandin E2 levels in the GI tissue but showed no significant change in LPS-treated mice. These findings indicate that the action of ghrelin binding to GHSR-1 improves endotoxemia-induced GI motility disturbances mainly through down-regulating the NO pathway in the GI tract.

Effects of serotonin on acid secretion in isolated rat stomach: the role of 5-HT3 receptors.

Serotonin (5-hydroxytryptamin; 5-HT) content has been measured using high-performance liquid chromatography with electrochemical detection (HPLC-ECD). The distributions of 5-HT-containing cells and 5-HT3 receptors have been determined with specific antibodies against 5-HT and 5-HT3 receptors, respectively. The effect of serotonin on acid secretion has been studied using an isolated rat stomach model. It has been shown that 5-HT concentrations in the fundus, mucosal layers of the corpus, remaining layer of the corpus and antrum are approximately 152, 498, 1494 and 972 nmol/mg protein, respectively. The distribution of 5-HT-containing cells is concentrated in the enteric plexus and enterochromaffin (EC) cells in the deep mucosal layer. Immunoreactivity to 5-HT3 receptors is localized in numerous neurons of the myenteric and submucosal plexus and concentrated in the neuronal plasma membrane, submucosa, endocrine cells and lamina propria. In the present study, the effect of 5-HT on gastric acid secretion was investigated on an everted preparation of isolated rat stomach. 5-HT at 1-100 microM reduced acid secretion stimulated by oxotremorine while 10 microM 5-HT did not modify the basal secretion of gastric acid. We further showed that 10 microM 5-HT reduced acid secretion and pepsin output stimulated by oxotremorine, histamine and pentagastrin; among the 5-HT receptors agonists tested, 2-methyl-5-HT (1-10 microM), a 5-HT3 receptor agonist, inhibited oxotremorine-, histamine- and pentagastrin-stimulated acid secretions, and this inhibitory effect was blocked by 1 microM MDL 72222, a specific 5-HT3 receptor antagonist. These results suggest that 5-HT is released from serotoninergic neurons, their processes and EC cells. The effect of 5-HT mediated by 5-HT3 receptors involves distinct neuronal and non-neuronal pathways which modulate gastric acid secretion.

Protective effects of Ginkgo biloba extract on the ethanol-induced gastric ulcer in rats.

AIM: To evaluate the preventive effect of Ginkgo biloba extract (GbE) on ethanol-induced gastric mucosal injuries in rats. METHODS: Female Wistar albino rats were used for the studies. We randomly divided the rats for each study into five subgroups: normal control, experimental control, and three experimental groups. The gastric ulcers were induced by instilling 1 mL 50% ethanol into the stomach. We gave GbE 8.75, 17.5, 26.25 mg/kg intravenously to the experimental groups respectively 30 min prior to the ulcerative challenge. We removed the stomachs 45 min later. The gastric ulcers, gastric mucus and the content of non-protein sulfhydryl groups (NP-SH), malondialdehyde (MDA), c-Jun kinase (JNK) activity in gastric mucosa were evaluated. The amount of gastric juice and its acidity were also measured. RESULTS: The findings of our study are as follows: (1) GbE pretreatment was found to provide a dose-dependent protection against the ethanol-induced gastric ulcers in rats; (2) the GbE pretreatment afforded a dose-dependent inhibition of ethanol-induced depletion of stomach wall mucus, NP-SH contents and increase in the lipid peroxidation (increase MDA) in gastric tissue; (3) gastric ulcer induced by ethanol produced an increase in JNK activity in gastric mucosa which also significantly inhibited by pretreatment with GbE; and (4) GbE alone had no inhibitory effect on gastric secretion in pylorus-ligated rats. CONCLUSION: The finding of this study showed that GbE significantly inhibited the ethanol-induced gastric lesions in rats. We suggest that the preventive effect of GbE may be mediated through: (1) inhibition of lipid peroxidation; (2) preservation of gastric mucus and NP-SH; and (3) blockade of cell apoptosis.

Function of GABAergic and glutamatergic neurons in the stomach.

Gamma-aminobutyric acid (GABA) and L-glutamic acid (L-Glu) are transmitters of GABAergic and glutamatergic neurons in the enteric interneurons, targeting excitatory or inhibitory GABA receptors or glutamate receptors that modulate gastric motility and mucosal function. GABAergic and glutamatergic neuron immunoreactivity have been found in cholinergic enteric neurons in the stomach. GABA and L-Glu may also subserve hormonal and paracrine signaling. Disruption in gastrointestinal function following perturbation of enteric GABA receptors and glutamate receptors presents potential new target sites for drug development.

Effect of lipopolysaccharide on diarrhea and gastrointestinal transit in mice: roles of nitric oxide and prostaglandin E2.

AIM: To investigate the effect of lipopolysaccharide (LPS) on the diarrheogenic activity, gastrointestinal transit (GIT), and intestinal fluid content and the possible role of nitric oxide (NO) and prostaglandin E2 (PGE2) in gastrointestinal functions of endotoxin-treated mice. METHODS: Diarrheogic activity, GIT, and intestinal fluid content as well as nitric oxide and PGE2 products were measured after intraperitoneal administration of LPS in mice. RESULTS: LPS dose-dependently accumulated abundant fluid into the small intestine, induced diarrhea, but decreased the GIT. Both nitric oxide and PGE2 were found to increase in LPS-treated mice. Western blot analysis indicated that LPS significantly induced the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 in mice intestines. Pretreatment with N(G)-nitro-L-arginine-methyl ester (L-NAME, a non-selective NOS inhibitor) or indomethacin (an inhibitor of prostaglandin synthesis) significantly attenuated the effects of LPS on the diarrheogenic activity and intestine content, but reversed the GIT. CONCLUSION: The present study suggests that the pathogenesis of LPS treatment may mediate the stimulatory effect of LPS on nitric oxide and PGE2 production and NO/prostaglandin pathway may play an important role on gastrointestinal function.

The possible role of heat shock factor-1 in the negative regulation of heme oxygenase-1.

We examined a possible role for heat shock factor-1 (HSF-1) in the negative regulation of HO-1 gene expression in human Hep3B hepatoma cells responding to stimulation with 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) and arsenite. Overexpression of HSF-1 and heat-shock experiments indicated that HSF-1 repressed the 15d-PGJ2-and arsenite-induced HO-1 gene expression through directly binding to the consensus heat shock element (HSE) of the HO-1 gene promoter. In addition, point mutations at specific HSE sequences of the HO-1 promoter-driven luciferase plasmid (pGL2/hHO3.2-Luc) abolished the heat shock- and HSF-1-mediated repression of reporter activity. Overall, it is possible that HSF-1 negatively regulates HO-1 gene expression, and that the HSE present in the -389 to -362 region mediates HSF-1-induced repression of human HO-1 gene expression.

Role of N-methyl-D-aspartate receptors in gastric mucosal blood flow induced by histamine.

Ionotropic N-methyl-D-aspartate (NMDA) receptor agonists, L-aspartic acid (L-Asp) and NMDA, have been shown to inhibit histamine-stimulated acid secretion, but their effect on gastric mucosal blood flow (GMBF) is largely unknown. The aim of this study was to investigate whether L-Asp and NMDA inhibit histamine-stimulated GMBF and to examine the expression patterns of NMDA receptor subunits NR1, NR2A, and NR2B in rat stomach. Laser Doppler flowmetry was used to measure gastric blood flow in anesthetized rats. The GMBF was assessed during an intravenous infusion of histamine in the presence of tripelennamine. The effects of L-Asp and NMDA on histamine-induced gastric blood flow were examined. In addition, the distribution patterns of NR1-, NR2A-, and NR2B-contaning NMDA receptors in rat stomach were determined immunohistochemically by using specific antibodies against NR1, NR2A, and NR2B. Histamine-induced enhancement of GMBF depended on acid secretion and the activation of H(2)-receptors. Neither L-Asp nor NMDA had an effect on the spontaneous GMBF. However, L-Asp and NMDA reduced the histamine-induced increase in GMBF. DL-2-amino-5-phosphonopentanoic acid (AP-5), an NMDA receptor antagonist; and prazosin, an alpha(1)-receptor antagonist; but not propanolol, a beta(2)-receptor antagonist; or yohimbine, a alpha(2)-receptor antagonist; reversed the inhibitory effect of L-Asp and NMDA on the histamine-induced increase in GMBF. Therefore, L-Asp and NMDA inhibit histamine-induced GMBF via a mechanism involving the activation of NMDA receptors and alpha(1)- adrenoceptors. The fact that NMDA receptor subunits NR1, NR2A, and NR2B were found to be localized in the rat stomach as visualized immunohistochemically with specific antibodies against NR1, NR2A, and NR2B is consistent with this hypothesis.