Gastrin CCK(2) receptor antagonists and locally active agents appear to represent promising therapies for the future. Development of gene targeting techniques has allowed production of genetically engineered transgenic and knockout mice.
Recently, there is a growing body of text that has been demonstrated by H 2 S that acts as a rescue molecule for mucosal defense. Till now the mechanisms underlying the gastroprotective effects of hydrogen sulfide were attributed to maintenance and/or elevation of gastric mucosal blood flow , stimulation of bicarbonate secretion , reduction of proinflammatory cytokine expression/release [9, 26], increase of prostaglandin synthesis , decrease of reactive oxygen metabolite production , and enhancement of tissue repair [8, 27]. The findings of the present study showed that the antisecretory effect of H 2 S could be the other possible protective mechanism. According to Figure 4, the gene expression of eNOS was significantly increased by NaHS and L-cysteine as compared with the corresponding controls.
The effects of a mast cell stabilizing agent, FPL 52694, on gastric acid secretion have been investigated in conscious dogs with gastric fistulae. This drug, given by intragastric instillation, inhibited acid output in response to submaximal infusions of pentagastrin and of histamine. A prolonged and significant fall in the acid concentration of the gastric juice was also observed. In the same animals, secretory inhibition by cimetidine was not accompanied by a sustained fall in acid concentration.
We studied the effects of NO on acid secretion induced by various stimulants in gastric glands isolated from stomach biopsies from human. Morphological examination of the hematoxylin-eosin-stained slides revealed that the isolation procedure had successfully yielded whole-gland preparations and that parietal cells were present in the gastric glands. Immunohistochemical analysis showed that the isolated glands contained eNOS-immunoreactive cells (Fig. 1), which agrees with results obtained using other types of mucosal preparations . Control experiments were primary antibody was excluded showed no immunoreactivity. Our results show that NO inhibits gastric acid secretion in isolated human gastric glands, and that there is endogenous formation of NO within the glandular epithelium in the vicinity of the parietal cells.
Whether a bitter-masking compound has opposite effects by causing gastric relaxation is an open question. The data presented here did not show any effects of HED on gastric secretion in humans, nor on proton secretion in HGT-1 cells at the concentrations tested. However, HED induced gastric relaxation, indicating physiological targets other than GAS. Caffeine, generally known as a stimulant of gastric acid secretion (GAS), is a bitter-tasting compound that activates several taste type 2 bitter receptors (TAS2Rs).
Furthermore, in a study of gastric glands isolated from stomach biopsies taken from humans , it was found that both histamine and db-cAMP induced secretory responses that were reproducible when repeated using gland preparations from the same subject, although there was considerable interindividual variation. Fellenius et al.  and Haglund et al.  have reported that both histamine and db-cAMP stimulated gastric acid secretion from isolated human gastric glands, and this was observed as a two- to threefold increase in AP accumulation compared to the background level. Those results agree with our data obtained using histamine and db-cAMP.
Various pharmaceuticals, such as histamine H 2 receptor (H 2 R) antagonists and H + /K + -ATPase (acid pump) inhibitors have been developed and utilized for the treatment of acid-related peptic diseases . All these results suggest the efficacy and safety of Hyptis spicigera in combating and healing gastric ulcer. Considering the results, it is suggested that the OEH could probably be a good therapeutic agent for the development of new phytotherapeutic medicine for the treatment of gastric ulcer. OEH chemical composition was analyzed by gas chromatography-mass spectrometry (GC-MS).
However, gastric function was severely affected by the loss of gastrin. Basal gastric acid secretion was abolished and could not be induced by histamine, carbachol, or gastrin. Histological analysis revealed alterations in the two cell types primarily involved in acid secretion, parietal and enterochromaffin-like (ECL) cells.
Such genetic technology has increased the investigative power for pharmacotherapy for not only antisecretory agents, but also treatment of mucosal diseases, such as atrophy, hyperplasia, and cancer. Elucidation of the origin of gastric parietal cells also represents an interesting investigative target that should allow a better understanding of not only acid-related diseases, but also the evolution of the stomach as an acid-secreting organ. This study compares the effects of lansoprazole and omeprazole on the activation and proliferation of enterochromaffin-like (ECL) cells in the rat stomach. Lansoprazole was given orally once daily for 10 weeks in two doses, 135 and 200 mumol/kg. Omeprazole was given by the same regimen in a dose of 400 mumol/kg, which is equipotent in terms of acid inhibition to the higher lansoprazole dose.
Patients received either 1200 mg proglumide or 1200 mg cimetidine per day for 28 days. The results showed that both drugs significantly reduced clinical symptoms and gastric secretion. In patients treated with cimetidine there was a significant increase in blood gastrin levels and marked hypertrophy and hyperplasia of the antral mucosa was observed in almost all patients. No such changes were found in the patients treated with proglumide.
L365,260 and L364,718 did not inhibit binding of radiolabeled vasoactive intestinal peptide, secretin, bombesin, substance P, or N-methylscopolamine to pancreatic acini. These results demonstrate that, in contrast to other gastrin-CCK receptor antagonists described, L365,260 is a selective gastrin receptor antagonist having an 80-fold higher affinity for gastrin than pancreatic CCK receptor, whereas L364,718 has a 125-fold higher affinity for pancreatic CCK receptors. Because of the selectivity of these two antagonists the involvement of CCK and gastrin in various physiological processes can be differentiated even when both receptors occur on the same cell. A double-blind trial was carried out in 30 patients with peptic ulcers to assess the effects of treatment with a gastrin-receptor antagonist, proglumide, compared with a histamine H2-blocker, cimetidine.
Antisecretory Effect of Hydrogen Sulfide on Gastric Acid Secretion and the Involvement of Nitric Oxide
and wild-type mice were measured at 18 days, 9 weeks, and 6 months of age as described previously (14). Mice were euthanized 15 min after subcutaneous injection of histamine (2 Î¼g/g body weight) and the intact stomach was removed. Although the plasma half-lives of PPIs are quite short, their mechanism of action enables most patients to be satisfactorily treated with once-daily dosing. Generally it does not matter whether the dose is given in the morning or the evening.
For the noninvasive measurement of gastric pH, the Heidelberg Detection System (Heidelberg Medical) was applied as described before (29, 30). When the subject arrived in the morning, the pH capsule was prepared by activation for 5 min in a sterile 0.9 NaCl solution and, as indicated by the Heidelberg Detection System software, the capsule was calibrated at pH 1 and pH 7. After calibration, the capsule was swallowed by the subject. When a pH of approximately 1-2 was stable over a period of 3 min, a stable position of the capsule in the stomach was considered to have been achieved. During the measurement, the subjects had to lie down on their left side to make sure that the capsule remained in the stomach.
Furthermore potentiating interactions occur between histamine, gastrin, and cholinergic agents which may account for the interdependence of secretagogue action observed in vivo. Direct potentiating interactions occur between histamine and gastrin and histamine and carbachol but not between carbachol and gastrin. However, in the presence of histamine, carbachol, and gastrin, a three-way potentiation does occur. By interfering with the potentiating interactions between stimulants, anticholinergic agents and cimetidine display an apparent cross-specificity in vitro that resembles the effects of these agents in intact mucosa.