Pepsinogen Secretion Research Articles

Dual role of nitric oxide in gastric hypersecretion in the distended stomach: Inhibition of acid secretion and stimulation of pepsinongen secretion

Aims We investigate the role of nitric oxide (NO) in the hypersecretion of acid and pepsinogen induced by stomach distension. Main method The rat stomach was distended by instillation of saline through an acute fistula under urethane anesthesia. Key findings Both secretions of acid and pepsinogen were increased by the distension depending on the volume of saline introduced, and responses were attenuated by bilateral cervical vagotomy or prior administration of atropine. N G-nitro- l-arginine methyl ester (L-NAME) had a dual effect on these responses, causing an increase in the acid response and a decrease in the pepsin response, both in an l-arginine-sensitive manner. Distension of the stomach increased the luminal NO release; this response was suppressed by vagotomy and L-NAME. Intragastric application of FK409, a NO donor, dose-dependently increased pepsinogen secretion while decreasing acid secretion in the stomach without distension. However, serosal application of both FK409 and 8-bromo-guanosine cyclic 3′, 5′-monophosphate (8-Br-cGMP) stimulated the secretion of pepsinogen in isolated mouse stomachs in vitro. The stimulatory effect of FK409 on pepsinogen secretion was totally abolished by LY83583, a guanylate cyclase inhibitor. Significance Distension of the stomach increases both acid and pepsinogen secretion through a vagal–cholinergic pathway in addition to the luminal release of NO, and NO affects these responses in opposite ways, suppressing the acid response while enhancing the pepsin response, both mediated by a guanylate cyclase/cGMP pathway.

Reaction of the gastric glands in wrestlers aged 7–32 years to threshold-power bicycle ergometer exercise

Problems of quick adaptation of the gastric glands of wrestlers to threshold-power bicycle ergometer exercise during sports and postsports ontogeny are discussed. It has been established that threshold-power bicycle ergometer exercise may suppress, stimulate, or not affect the secretion of H2O, HCl, and pepsinogen. The pattern of these shifts is aimed at optimizing the actual level of protein hydrolysis; it depends on the age, sports experience, and qualification and is correlated with the body weight.

An immunohistochemical study of endocrine cells in the iodoacetamine-induced rat's gastritis

The gastric epithelium is a complex stucture formed by tubular gastric glands. The gastric glands contain a wide variety of cell types according to the secretion of hydrochloric acid, proteases, mucus, pepsinogen and hormones. Endocrine and local paracrine mediators are of crucial importance for maintaining structural and functional integrity of the epithelium. Therefore our aim was to investigate the precise localization and density of the endocrine cells and their contacts in iodoacetamine-induced rat's gastritis. Methods: somatostatin (SOM), calcitonin gene-related peptide CGRP), substance P (SP), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY) and galanin immunoreactive (IR) endocrine cells and nerve elements were detected by ABC immunohistochemistry. Results: The quantitative analysis of the density of the different neuropeptide containing endocrine cells and nerve fibres showed that the (IR) nerve fibres were found with different density. The number of SOM and CGRP IR endocrine cells increased significantly in the gastritis. Both endocrine cells possessed long cytoplasmic extensions and no cell-to-cell contact between parietal and endocrine cells was found. The number of SP, VIP, NPY IR nerve fibres also increased significantly in the gastritis, however, the others showed no alteration. The number of the immunocompetent cells was also increased (being lymphocytes, plasma cells and mast cells) and 16,8% of the immunocytes were IR for SP and 9, 4% of them were IR for NPY. In several cases close contacts were detected between IR nerve fibres and the immunocytes. Conclusions: The increased number of SOM and CGRP endocrine cells and SP IR nerve fibres might play a crucial role in the regulation of gastric acid secretion, including gastric ulcer disease and autoimmune gastritis. The main inhibitor of acid secretion is somatostatin. CGRP activates the mucin biosynthesis, both SOM and CGRP have a preventive action on gastric mucosal injury. The changes in the density of nerve fibres and immunocytes might be the consequences of the inflammation.

IL-1β and IL-8, matrix metalloproteinase 3, and pepsinogen secretion before and after H. pylori eradication in gastroduodenal phenotypes

Objective. Relations between host genetic factors and clinical outcomes of Helicobacter pylori infection are variable among ethnicities. The aim of this study was to examine gastric mucosal cytokines, matrix metalloproteinase 3 (MMP-3), and serum pepsinogen levels before and after eradication of H. pylori according to IL-1B genotypes and benign gastroduodenal phenotypes in a Korean population. Material and methods. A total of 349 Koreans including H. pylori-infected subjects (n=230) and H. pylori-negative controls (n=119) were enrolled. The former subjects were classified into groups according to the presence of non-atrophic gastritis (n=74), atrophic gastritis (n=56), gastric ulcer (n=37), and duodenal ulcer (n=63). IL-1B polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Gastric mucosal IL-1β, IL-8, and MMP-3, and serum pepsinogen I and II levels were measured by ELISA and radioimmunoassay, respectively. Results. There were no significant differences between the IL-1B–31/–511 haplotype (TT/CC, CT/CT, and CC/TT) frequencies among the H. pylori-positive and −negative groups. The genotypes of IL-1B–31/–511 polymorphisms did not affect clinical phenotypes, inflammatory cytokines, MMP-3, and pepsinogen secretion. Subjects with H. pylori-infected atrophic gastritis exhibited significantly higher basal levels of cytokines and a lower pepsinogen I/II ratio than those of other groups. Following H. pylori eradication, inflammatory cytokines significantly decreased and the pepsinogen I/II ratio increased in all groups. Conclusions. Mucosal inflammatory cytokines, MMP-3, and pepsinogen secretion are related to gastroduodenal phenotypes but not to IL-1B genotypes. Eradication of H. pylori can reduce mucosal inflammation and restore pepsinogen secretion.

Cholecystokinin, Carbachol のモルモット遊離胃主細胞内Ca++濃度調節作用に関する研究

Cholecystokinin, Carbachol のモルモット遊離胃主細胞内Ca++濃度調節作用に関する研究

The vertebrate animal gut in context ? microbiomes, metagenomes and methane

The microbial world colonises the gastrointestinal tracts of vertebrates soon after birth or hatching. These animal-microbe relationships have been described as competitive, cooperative or combinatorial, and all provide a variety of functional and metabolic capabilities that are relevant to host animal nutrition, health and well-being. The evolutionary adaptations of Australia?s marsupial herbivores have been relatively well characterised and favour both the cooperative and combinatorial animal-microbe models. Kangaroos and wallabies possess the cooperative model: the foregut functions as an obligate combustion chamber for a microbiome specialised in the release of nutrients from plant biomass, and which precedes a region of acid and pepsinogen secretions by the host. The common ringtail possum and wombats are examples of Australian herbivores with specialised caecal and colonic obligate combustion chambers, respectively. As such, these animals typify the combination model of animal-microbe association: the stomach and its associated digestive processes precede the obligate combustion chamber and its resident microbiome that coordinates the enzymatic hydrolysis and fermentation of plant biomass.

Roles of Protease-Activated Receptor-2 (PAR-2), a G Protein-Coupled Receptor, in Modulation of Exocrine Gland Functions

Protease-activated receptor-2 (PAR-2), a G protein-coupled receptor, is activated by proteolytic unmasking of the N-terminal extracellular tethered ligand that presumably binds to the extracellular loop 2 of the receptor itself. PAR-2 is widely distributed in the mammalian body and plays various roles in biological events in the cardiovascular, respiratory, alimentary, and central neurons systems. PAR-2-activating peptides administered systemically to mice and rats trigger prompt salivation in vivo. In an in vitro study, PAR-2 agonists including the endogenous PAR-2 activator trypsin induce secretion of amylase and mucin from isolated rat parotid glands and sublingual glands, respectively. PAR-2-activating peptides administered systemically also modulate pancreatic exocrine secretion in vivo as well as in vitro. In the gastric mucosa, PAR-2 stimulation enhances secretion of mucus and pepsinogen and suppresses acid secretion. Tear secretion can also be caused by PAR-2-related peptides in PAR-2-dependent and -independent manners. PAR-2 thus plays a general or key role in the regulation of exocrine secretion. This review focuses on the physiologic and/or pathophysiologic roles of PAR-2 in glandular exocrine secretion. The possibility of PAR-2 as a target for drug development is also discussed.

Role of Na-K-2Cl cotransporter-1 in gastric secretion of nonacidic fluid and pepsinogen

Na-K-2Cl cotransporter-1 (NKCC) has been detected at exceptionally high levels in the gastric mucosa of several species, prompting speculation that it plays important roles in gastric secretion. To investigate this possibility, we 1) immunolocalized NKCC protein in the mouse gastric mucosa, 2) compared the volume and composition of gastric fluid from NKCC-deficient mice and their normal littermates, and 3) measured acid secretion and electrogenic ion transport by chambered mouse gastric mucosa. NKCC was localized to the basolateral margin of parietal cells, mucous neck cells, and antral base cells. In NKCC-deficient mice, gastric secretions of Na+, K+, Cl-, fluid, and pepsinogen were markedly impaired, whereas secretion of acid was normal. After stimulation with forskolin or 8-bromo-cAMP, chambered corpus mucosa vigorously secreted acid, and this was accompanied by an increase in transmucosal electrical current. Inhibition of NKCC with bumetanide reduced current to resting levels but had no effect on acid output. Although prominent pathways for basolateral Cl- uptake (NKCC) and apical Cl- exit [cystic fibrosis transmembrane conductance regulator (CFTR)] were found in antral base cells, no impairment in gastric secretion was detected in CFTR-deficient mice. Our results establish that NKCC contributes importantly to secretions of Na+, K+, Cl-, fluid, and pepsinogen by the gastric mucosa through a process that is electrogenic in character and independent of acid secretion. The probable source of the NKCC-dependent nonacidic electrogenic fluid secretion is the parietal cell. The observed dependence of pepsinogen secretion on NKCC supports the concept that a nonacidic secretory stream elaborated from parietal cells facilitates flushing of the proenzyme from the gastric gland lumen.

Cholinergic agonist-induced pepsinogen secretion from murine gastric chief cells is mediated by M1and M3muscarinic receptors

Muscarinic cholinergic mechanisms play a key role in stimulating gastric pepsinogen secretion. Studies using antagonists suggested that the M3 receptor subtype (M3R) plays a prominent role in mediating pepsinogen secretion, but in situ hybridization indicated expression of M1 receptor (M1R) in rat chief cells. We used mice that were deficient in either the M1 (M1R-/-) or M3 (M3R-/-) receptor or that lacked both receptors (M(1/3)R-/-) to determine the role of M1R and M3R in mediating cholinergic agonist-induced pepsinogen secretion. Pepsinogen secretion from murine gastric glands was determined by adapting methods used for rabbit and rat stomach. In wild-type (WT) mice, maximal concentrations of carbachol and CCK caused a 3.0- and 2.5-fold increase in pepsinogen secretion, respectively. Maximal carbachol-induced secretion from M1R-/- mouse gastric glands was decreased by 25%. In contrast, there was only a slight decrease in carbachol potency and no change in efficacy when comparing M3R-/- with WT glands. To explore the possibility that both M1R and M3R are involved in carbachol-mediated pepsinogen secretion, we examined secretion from glands prepared from M(1/3)R-/- double-knockout mice. Strikingly, carbachol-induced pepsinogen secretion was nearly abolished in glands from M(1/3)R-/- mice, whereas CCK-induced secretion was not altered. In situ hybridization for murine M1R and M3R mRNA in gastric mucosa from WT mice revealed abundant signals for both receptor subtypes in the cytoplasm of chief cells. These data clearly indicate that, in gastric chief cells, a mixture of M1 and M3 receptors mediates cholinergic stimulation of pepsinogen secretion and that no other muscarinic receptor subtypes are involved in this activity. The development of a murine secretory model facilitates use of transgenic mice to investigate the regulation of pepsinogen secretion.

Pepsinogen and H,K-ATPase mediate acid secretion in gastric glands of Triturus carnifex (Amphibia, Caudata)

The gastric glands of Triturus carnifex (Amphibia, Caudata) have been examined by histochemical and immunohistochemical methods with particular regard to hydrochloric acid and pepsinogen secretion. Fundic glands consist of mucous neck cells, endocrine cells and oxynticopeptic cells producing both pepsinogen and hydrochloric acid. The neck cells showed an unexpected distribution pattern which was only observed in the oral fundus, and produced neutral mucins with glycosidic residues of GalNAc and Gal beta1,3GalNAc, and in this respect they differ from the neck cells of anuran amphibians. The secretion of pepsinogen and hydrochloric acid as demonstrated by immunolabelling with anti-H,K-ATPase and with anti-pepsinogen, respectively, seems not to vary significantly along the longitudinal axis of the stomach. The mechanism of gastric acid secretion seems to be mediated by an ATPase, having similar features to the mammalian gastric H,K-ATPase, and is localised in the luminal membrane and in the subapical cytoplasm of the oxynticopeptic cells. Unusually, the same cytoplasmic areas revealed binding specificity for the winged pea lectin (WPA) from Lotus tetragonolobus, even after beta elimination, indicating the presence of fucosyl residues in N-linked oligosaccharidic chains in glycoproteins of beta-H,K-ATPase subunits.

PAR2 as a target for gastric mucosal protection

Protease-activated receptors (PARs), especially PAR2, are abundantly expressed throughout the gastrointestinal tract, including the stomach. PAR2 plays multiple roles in the modulation of gastric functions. Exogenously applied PAR2 agonists stimulate the secretion of gastric mucus and pepsinogen, suppress gastric acid output, enhance gastric mucosal blood flow and modulate the motility of gastric smooth muscle. Most of these gastric functions of PAR2, except for the stimulation of pepsinogen secretion, are thus protective in the stomach. Indeed, PAR2 agonists protect against gastric mucosal lesions induced by ethanol/HCI or indomethacin in laboratory animals. The PAR2-mediated protective mechanisms appear to primarily involve activation of capsaicin-sensitive sensory nerves in the gastric mucosa, although PAR2 stimulation would also trigger activation of other multiple pathways. PAR2 would thus appear to be a novel target for the development of drugs for the treatment of gastric mucosal diseases.

Working Outside the Cell

Many signaling molecules interact with cell surface receptors to mobilize calcium from intracellular stores, eliciting transient changes in the concentration of intracellular calcium ([Ca 2+ ] i ), which acts as a second messenger. Mobilized cytoplasmic Ca 2+ extruded through plasma membrane Ca 2+ ATPases can increase local extracellular Ca 2+ concentration [Ca 2+ ] o, whereas store-operated Ca 2+ entry can lead to a localized decrease in [Ca 2+ ] o . Indeed, in gastric epithelial cells, the cholinergic agonist carbachol elicits a simultaneous increase in lumenal [Ca 2+ ] o and decrease in serosal [Ca 2+ ] o , because of the polarized distribution of Ca 2+ -handling molecules. Using a proteolytic assay to measure pepsinogen secretion, and ion-sensitive microelectrodes to measure pH and [Ca 2+ ], Caroppo et al. investigated the effects of changing [Ca 2+ ] o on alkaline secretion and pepsinogen secretion in isolated frog gastric mucosa. Simultaneous changes in lumenal and serosal [Ca 2+ ] o comparable to those elicited by carbachol stimulated comparable secretion of pepsinogen and changes in gastric gland lumenal pH. Increasing only lumenal [Ca 2+ ] o had a smaller effect on secretion, whereas decreasing serosal [Ca 2+ ] o alone was ineffective. Pharmacological analysis implicated a previously identified extracellular Ca 2+ receptor (CaR) in the response; moreover, citrate, added to buffer lumenal [Ca 2+ ] o , prevented both the carbachol-dependent increase in lumenal [Ca 2+ ] o and alkaline and pepsinogen secretion. In contrast, stimulating CaR pharmacologically or increasing lumenal [Ca 2+ ] o did not affect [Ca 2+ ] i , as measured either with intracellular microelectrodes or indirectly through activation of a Ca 2+ -sensitive K + current. Thus, the authors propose that, in this system, changes in [Ca 2+ ] o after Ca 2+ mobilization from intracellular stores can act as a third messenger to stimulate secretion. R. Caroppo, A. Gerbino, G. Fistetto, M. Colella, L. Debellis, A. M. Hofer, S. Curci, Extracellular calcium acts as a "third messenger" to regulate enzyme and alkaline secretion. J. Cell Biol . 166 , 111-119 (2004). [Abstract] [Full Text]

Extracellular calcium acts as a "third messenger" to regulate enzyme and alkaline secretion.

It is generally assumed that the functional consequences of stimulation with Ca2+-mobilizing agonists are derived exclusively from the second messenger action of intracellular Ca2+, acting on targets inside the cells. However, during Ca2+ signaling events, Ca2+ moves in and out of the cell, causing changes not only in intracellular Ca2+, but also in local extracellular Ca2+. The fact that numerous cell types possess an extracellular Ca2+ “sensor” raises the question of whether these dynamic changes in external [Ca2+] may serve some sort of messenger function. We found that in intact gastric mucosa, the changes in extracellular [Ca2+] secondary to carbachol-induced increases in intracellular [Ca2+] were sufficient and necessary to elicit alkaline secretion and pepsinogen secretion, independent of intracellular [Ca2+] changes. These findings suggest that extracellular Ca2+ can act as a “third messenger” via Ca2+ sensor(s) to regulate specific subsets of tissue function previously assumed to be under the direct control of intracellular Ca2+.

The PAR-1-activating peptide facilitates pepsinogen secretion in rats

Protease-activated receptor-2 (PAR-2) is abundantly expressed in gastric mucosal chief cells, facilitating pepsinogen secretion. In the present study, we investigated whether PAR-1, a thrombin receptor, could modulate pepsinogen secretion in rats. The PAR-1-activating peptide TFLLR-NH 2 as well as the PAR-2-activating peptide SLIGRL-NH 2, administered i.v. repeatedly at 1-h intervals, significantly increased gastric pepsinogen secretion over 2–4 h (after two to four doses). In contrast, the control peptide FTLLR-NH 2, given in the same manner, had no such effect. Thus, PAR-1, like PAR-2, might function to facilitate pepsinogen secretion, suggesting a novel role of the thrombin-PAR-1-pathway in the stomach.

Modulation of gastric function by proteinase‐activated receptors

AbstractProteinase‐activated receptor (PAR)1 and PAR2 are abundantly expressed in the gastric mucosa and smooth muscle. PAR2 modulates a variety of gastric functions, mediating secretion of mucus and pepsinogen, suppression of acid output, an increase in mucosal blood flow, and smooth muscle contraction/relaxation. PAR2 is considered primarily protective in the gastric mucosa. PARs other than PAR2 might also be involved in the modulation of gastric functions. PARs, especially PAR2, would thus appear to be novel targets for the development of drugs for treatment of gastric mucosal diseases. Drug Dev. Res. 60:9–13, 2003. © 2003 Wiley‐Liss, Inc.

PAR-2 modulates pepsinogen secretion from gastric-isolated chief cells.

In the present study, we investigated whether activation of protease-activated receptor type 2 (PAR-2) with SLIGRL (SL)NH2, a short mimetic agonistic peptide, directly stimulates pepsinogen secretion from gastric-isolated, pepsinogen-secreting (chief) cells. Immunostaining of gastric-dispersed chief cells with a specific anti-PAR-2 antibody demonstrated expression of PAR-2 receptors on membrane and cytoplasm. SL-NH2 and trypsin potently stimulated pepsinogen secretion (EC50 = 0.3 nM) and caused Ca2+ mobilization (EC50 = 0.6 nM). In contrast to SL-NH2, the scramble peptide LSIGRL-NH2 failed to stimulate pepsinogen release. Exposure to SL-NH2 also resulted in ERK1/2 phosphorylation and activation. Exposure of chief cells to phosphotyrosine kinase inhibitors and 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one, a selective MEK inhibitor, significantly reduced secretion induced by SL-NH2. Pepsinogen secretion induced by SL-NH2 was desensitized by pretreating the cells with the mimetic peptide and trypsin, and exposure to SL-NH2 abrogates pepsinogen secretion induced by carbachol and CCK-8, but not secretion induced by secretin and vasointestinal peptide. Exposure to Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 (substance P) but not to calcitonin gene-related peptide increased pepsinogen release. The neurokinin-1 receptor antagonist, N-acetyl-l-tryptophan 3,5-bis(trifluoromethyl)benzyl ester, inhibited substance P-stimulated pepsinogen secretion, whereas it did not affect secretion induced by SL-NH2. Collectively, these data indicate that PAR-2 is expressed on gastric chief cells and that its activation causes a Ca2+-ERK-dependent stimulation of pepsinogen secretion.

The M1 muscarinic receptor is required for full expression of cholinergic agonist-induced pepsinogen secretion

The M1 muscarinic receptor is required for full expression of cholinergic agonist-induced pepsinogen secretion

Smoking and the pathogenesis of gastroduodenal ulcer--recent mechanistic update.

Peptic ulcer is a common disorder of gastrointestinal system and its pathogenesis is multifactorial, where smoking and nicotine have significant adverse effects. Smoking and chronic nicotine treatment stimulate basal acid output which is more pronounced in the smokers having duodenal ulcer. This increased gastric acid secretion is mediated through the stimulation of H2-receptor by histamine released after mast cell degranulation and due to the increase of the functional parietal cell volume or secretory capacity in smokers. Smoking and nicotine stimulate pepsinogen secretion also by increasing chief cell number or with an enhancement of their secretory capacity. Long-term nicotine treatment in rats also significantly decreases total mucus neck cell population and neck-cell mucus volume. Smoking also increases bile salt reflux rate and gastric bile salt concentration thereby increasing duodenogastric reflux that raises the risk of gastric ulcer in smokers. Smoking and nicotine not only induce ulceration, but they also potentiate ulceration caused by H. pylori, alcohol, nonsteroidal anti-inflammatory drugs or cold restrain stress. Polymorphonuclear neutrophils (PMN) play an important role in ulcerogenesis through oxidative damage of the mucosa by increasing the generation of reactive oxygen intermediates (ROI), which is potentiated by nicotine and smoking. Nicotine by a cAMP-protein kinase A signaling system elevates the endogenous vasopressin level, which plays an aggressive role in the development of gastroduodenal lesions. Smoking increases production of platelet activating factor (PAF) and endothelin, which are potent gastric ulcerogens. Cigarette smoking and nicotine reduce the level of circulating epidermal growth factor (EGF) and decrease the secretion of EGF from the salivary gland, which are necessary for gastric mucosal cell renewal. Nicotine also decreases prostaglandin generation in the gastric mucosa of smokers, thereby making the mucosa susceptible to ulceration. ROI generation and ROI-mediated gastric mucosal cell apoptosis are also considered to be important mechanism for aggravation of ulcer by cigarette smoke or nicotine. Both smoking and nicotine reduce angiogenesis in the gastric mucosa through inhibition of nitric oxide synthesis thereby arresting cell renewal process. Smoking or smoke extract impairs both spontaneous and drug-induced healing of ulcer. Smoke extract also inhibits gastric mucosal cell proliferation by reducing ornithine decarboxylase activity, which synthesises growth-promoting polyamines. It is concluded that gastric mucosal integrity is maintained by an interplay of some aggressive and defensive factors controlling apoptotic cell death and cell proliferation and smoking potentiates ulcer by disturbing this balance.

Multiple roles for protease-activated receptor-2 in gastric mucosa

Protease-activated receptor-2 (PAR-2), a G-protein-coupled receptor, is activated by proteolytic unmasking of the N-terminal cryptic tethered ligand. In gastric mucosa, activation of PAR-2 expressed by sensory neurons triggers release of CGRP and tachykinins, leading to mucus secretion via activation of CGRP1 and NK2 receptors, respectively. The PAR-2 agonist reveals mucosal cytoprotective effects in several gastric injury models. Further, PAR-2 activation inhibits gastric acid secretion, independently of sensory neurons or prostanoid formation. The PAR-2 agonist also induces increase in gastric mucosal blood flow, an effect being independent of endogenous CGRP or NO. Endothelium-derived hyperpolarizing factor (EDHF) appears to be involved in the PAR-2-mediated enhancement of mucosal blood flow. In contrast, mucosal chief cells are abundant in immunoreactive PAR-2, and PAR-2 stimulation triggers pepsinogen secretion. Taken together, primarily, PAR-2 plays protective roles in gastric mucosa through multiple mechanisms. Considering PAR-2-mediated pepsinogen secretion, PAR-2 might function as a double-edged sword in gastric mucosa.

EFFECTS OF A BICARBONATE-ALKALINE MINERAL WATER ON GASTRIC FUNCTIONS AND FUNCTIONAL DYSPEPSIA: A PRECLINICAL AND CLINICAL STUDY

The present study was performed in order to evaluate: (1) the influence of a bicarbonate-alkaline mineral water (Uliveto ®) on digestive symptoms in patients with functional dyspepsia; (2) the effects of Uliveto ® on preclinical models of gastric functions. Selected patients complained of dyspeptic symptoms in the absence of digestive lesions or Helicobacter pylori infection within the previous 3 months. They were treated with Uliveto ® water (1.5 l day −1) for 30 days. Frequency and severity of symptoms were assessed at baseline and day 30 by a score system. Preclinical experiments were carried out on rats, allowed to drink Uliveto ® or oligomineral water for 30 days. Animals then underwent pylorus ligation to evaluate gastric secretion of acid, pepsinogen, and mucus. In separate experiments, gastric emptying was assessed. Crenotherapy was associated with a relief of epigastric pain, retrosternal pyrosis, postprandial fullness and gastric distention. At preclinical level, Uliveto ® water increased acid and pepsinogen secretions as well as gastric emptying, without changes in bound mucus. The enhancing actions of Uliveto ® on gastric secretions and emptying were prevented by L-365,260, an antagonist of gastrin/CCK-2 receptors. These findings indicate that a regular intake of Uliveto ® favors an improvement of dyspeptic symptoms. The preclinical study suggests that the clinical actions of Uliveto ® water depend mainly on its ability to enhance gastric motor and secretory functions.