vasoactive-intestinal-peptide and Stomach-Ulcer

Somatostatin is located predominantly in D-cells of the antral and fundic area of the stomach and in the duodenal bulb. Furthermore, somatostatin is contained in neurons of the extrinsic and intrinsic nervous system. Somatostatin inhibits gastric acid, pepsin and gastrin secretion, and it stimulates gastric mucous secretion. All in all, somatostatin could exert protection of the gastric mucosa by reduction of aggressive and augmentation of protective mechanisms. There is, however, no evidence for a role of somatostatin in the pathogenesis of peptic ulcer. Endogenous opioids which have to be considered as potential peptidergic neurotransmitters increase vagal and postprandial gastric acid secretion and accordingly cannot be considered as a protective factor. Vasoactive intestinal peptide (VIP), also a peptidergic neurotransmitter, reduces acid and stimulates mucous and bicarbonate secretion. If this is of physiological relevance remains to be established. Secretin might be a protective factor for the gastric mucosa by stimulating mucous and bicarbonate secretion. On the other hand, it augments pepsin secretion which might attenuate any potential protective effects of secretin.

Topics: Animals; Endorphins; Gastric Mucosa; Humans; Secretin; Somatostatin; Stomach Ulcer; Vasoactive Intestinal Peptide

Topics: Cimetidine; Duodenal Ulcer; Gastric Juice; Gastric Mucosa; Gastrins; Glycoproteins; Humans; Intestinal Mucosa; Peptic Ulcer; Receptors, Histamine; Secretin; Secretory Rate; Somatostatin; Stomach Ulcer; Vasoactive Intestinal Peptide

Citrus lemon (CL) belongs to Rutaceae family and is popularly known in Brazil as limão siciliano. The phytochemical analysis of CL fruit bark essential oil showed two majority components, limonene (LIM) and β-pinene (PIN). This study aimed to evaluate the gastroprotective mechanism of action from CL, LIM and PIN in ethanol- and indomethacin-induced gastric ulcers and its in vitro anti-Helicobacter pylori activity. After ethanol-induced gastric ulcer, the ulcer area was measured and the stomachs were destined to histology (HE and PAS), immunohistochemistry for HSP-70 and VIP and glutathione (GSH) measurement. The involvement of nitric oxide (NO) and sulfhydryl (SH) compounds was determined. The ulcer area for indomethacin-induced gastric ulcers was measured. PGE₂ concentration was biochemically measured. The minimum inhibitory concentration (MIC) against H. pylori was determined in vitro. In ethanol model, CL and LIM demonstrated 100% of gastroprotection, while PIN did not exert effective gastroprotection (53.26%). In the indomethacin model, CL and LIM offered effective gastroprotection but PIN did not show gastroprotective effect. The gastric ulcer area of rats pretreated with NO-synthase inhibitor or SH-blocker was decreased in comparison to the control group. The MIC obtained for CL was 125 μg/mL, for LIM was 75 μg/mL and for PIN was 500 μg/mL. The gastroprotective effect of CL and LIM was involved with increasing in mucus secretion, HSP-70 and VIP, but not with GSH, NO or SH compounds. CL gastroprotective mechanism is involved with PGE₂. PIN did not present gastroprotective activity.

Topics: Animals; Bicyclic Monoterpenes; Bridged Bicyclo Compounds; Citrus; Cyclohexenes; Dinoprostone; Disease Models, Animal; Drug Synergism; Glutathione; Helicobacter Infections; Helicobacter pylori; HSP70 Heat-Shock Proteins; Immunohistochemistry; Limonene; Male; Microbial Sensitivity Tests; Monoterpenes; Nitric Oxide; Plant Oils; Protective Agents; Rats; Rats, Wistar; Stomach Ulcer; Sulfhydryl Compounds; Terpenes; Vasoactive Intestinal Peptide

This study aimed to evaluate the gastroprotective mechanism of action of the essential oil of Croton cajucara Benth. (Euphorbiaceae) stem bark in ethanol-induced gastric ulcers and its in vitro anti-Helicobacter pylori activity. The involvement of heat-shock protein-70, vasoactive intestinal peptide, glutathione, nitric oxide, and nonprotein sulfhydryl compounds in the gastroprotective effect was determined in male Wistar rats. The minimum inhibitory concentration against H. pylori was determined in vitro. The results were analyzed by analysis of variance followed by the Dunnett test, and a P value less than 0.05 was considered to represent a statistically significant difference. C. cajucara decreased ethanol-induced ulcer area in 100% of ulcers and decreased the histologic lesions. In the C. cajucara group, the area marked by heat-shock protein-70 was significantly higher than the area in the control group; this finding was not seen for vasoactive intestinal peptide. C. cajucara could not maintain glutathione levels close to those in the sham group. The gastric ulcer area of rats treated with the sulfhydryl compound blocker was decreased, but the ulcer area of rats treated with nitric oxide synthase inhibitor showed no alteration. The minimum inhibitory concentration obtained for C. cajucara was 125 μg/mL. These findings suggest that sulfhydryl compounds and heat-shock protein-70, but not nitric oxide, glutathione, or vasoactive intestinal peptide, are involved in the C. cajucara gastroprotective effect against ethanol-induced gastric ulcers.

Topics: Animals; Anti-Bacterial Agents; Anti-Ulcer Agents; Croton; Gastric Mucosa; Glutathione; Helicobacter pylori; HSP70 Heat-Shock Proteins; Male; Medicine, Traditional; Microbial Sensitivity Tests; Nitric Oxide; Oils, Volatile; Plant Bark; Plant Stems; Rats; Rats, Wistar; South America; Stomach Ulcer; Sulfhydryl Compounds; Vasoactive Intestinal Peptide

Vasoactive intestinal peptide (VIP) prevents stress-induced gastric ulcers, inhibits mast cell degranulation and protects gastric tissue from lipid peroxidation. Histamine has an important role in the development of gastric ulcers and mast cell derived histamine might be essential in this process.

Topics: Animals; Female; Gastric Mucosa; Histamine; Male; Methylation; Rats; Rats, Sprague-Dawley; Stomach Ulcer; Stress, Physiological; Vasoactive Intestinal Peptide

Pituitary adenylate cyclase activating peptide and vasoactive intestinal peptide belong to the same neuropeptide family. Both peptides are present in nerve fibers in the gastric wall and are thought to be involved in the regulation of inflammatory processes. Experimental ulcers were induced in the rat gastric mucosa by local application of acetic acid. During the healing process we examined the PACAP and VIP innervation by means of immunohistochemistry and in situ hybridization. The ulcer area was examined from day 1 to day 15 after ulcer induction. There was a marked depletion of PACAP in nerve fibers at the ulcer margin from day 1 and onwards. On day 10 and day 15, PACAP-immunoreactive nerve fibers could again be visualized at the ulcer margin. In contrast, VIP immunoreactive nerve fibers were present at the ulcer margin at all time points studied. From day 10 following ulcer induction PACAP- and VIP- immunoreactive nerve fibers were increased in frequency in the smooth muscle beneath the ulcer. An upregulation of VIP and PACAP mRNA was also demonstrated in the myenteric ganglia adjacent to ulcer. The present results indicate that neuronal PACAP and VIP react differently to the inflammation at the ulcer margin but similarly in the smooth muscle during the ulcer healing.

Topics: Animals; Female; Gastric Mucosa; Immunohistochemistry; In Situ Hybridization; Myenteric Plexus; Neuropeptides; Neurotransmitter Agents; Parietal Cells, Gastric; Pituitary Adenylate Cyclase-Activating Polypeptide; Rats; Rats, Sprague-Dawley; RNA, Messenger; Stomach Ulcer; Up-Regulation; Vasoactive Intestinal Peptide

The pathogenesis of cold-restraint stress ulcer involves various factors and is not completely understood. Mast cell degranulation, increased gastric muscular contractility, diminished mucosal blood flow, release of several biogenic amines, activated polymorphonuclear leukocytes, and lipid peroxidation which results from toxic oxygen molecules were suggested to be related to the production of gastric damage by cold-restraint stress. Recent evidence strongly indicates that VIP has a modulatory effect on tissue injury. Sprague-Dawley rats were used in two series of experiments. One set of rats was exposed to cold-restraint stress with some of the rats pretreated with VIP. The second set of rats was exposed to cold-restraint stress and then was administered VIP for different durations. Cold-restraint stress induced gastric lesions and mast cell degranulation and also increased lipid peroxidation in gastric tissue. VIP prevented stress-induced ulcers and mast cell degranulation and protected gastric tissue from lipid peroxidation. When VIP was used after induction of stress ulcer it was therapeutically beneficial. Thanks to its antioxidant and anti-inflammatory activity, VIP can be valuable in the prevention of gastric mucosal damage induced by cold-restraint stress.

Topics: Animals; Catalase; Cell Degranulation; Female; Gastric Mucosa; Male; Malondialdehyde; Mast Cells; Rats; Rats, Sprague-Dawley; Restraint, Physical; Stomach Ulcer; Stress, Psychological; Superoxide Dismutase; Vasoactive Intestinal Peptide

Using an immunohistochemical technique, the presence and distribution of vasoactive intestinal polypeptide (VIP) was investigated in cryostat sections, both tangential and transverse, of the fetal pig's stomach. In all fetuses and in all gastric segments investigated, VIP-like immunoreactive (IR) nerve-cell bodies were seen in all intramural ganglia, and VIP-IR nerve fibres were found in all layers of the gastric wall except the tunica serosa. Consequently, VIP-IR nerve fibres were found to form a periglandular network, to accompany arterioles, to interconnect the intramural ganglia, to encircle both VIP-IR-negative and -positive neurons, and were found in all muscle layers. Despite the fact that VIP-IR seems to be restricted to the intramural nervous elements, some non-specific-reacting VIP-IR glandular cells were noticed in the basal parts of the fundic, antral and pyloric gastric glands. The distribution pattern of VIP in the fetal pig resembles that of the adult pig. This suggests a possible functional role for VIP during fetal life and/or puts forward the suggestion that the stomach of a fetal pig from the second half of the gestation period is prepared, from then on, for postnatal function. High similarities with regard to the general distribution pattern of VIP in the stomach have also been noted between the fetal pig and humans, proving once more that the fetal pig can serve as a good animal model in several research areas. Finally, the morphological data provided here may, combined with the physiological significance of VIP, contribute to a better insight into the physiopathology of economically important gastro-intestinal disorders in the pig, such as gastric ulceration.

Topics: Animals; Disease Models, Animal; Fetus; Immunohistochemistry; Nerve Fibers; Neurons; Stomach; Stomach Ulcer; Swine; Swine Diseases; Vasoactive Intestinal Peptide

Basic fibroblast growth factor (bFGF) has well-established angiogenic and ulcer healing actions. bFGF has also been found to induce neural regeneration in the central nervous system. Thus, the present study was undertaken to clarify the effect of basic fibroblast growth factor on the regeneration of autonomic nerves in the granulation tissues following the induction of experimental gastric ulcer induced by acetic acid in rats. Rats were divided into control, acetic acid alone, and acetic acid plus acid-stable human recombinant basic fibroblast growth factor (CS23, 1 microgram/100 g body wt., every 12 hr for three days, or one or two weeks, through oral gastric intubation) groups. As a result, few autonomic nerves were recognized surrounding the newly formed arterioles and venules in the acetic acid alone group. In the CS23-treated group, the cholinergic, calcitonin gene-related peptide and vasoactive intestinal peptide-immunoreactive nerves were clearly recognized near the microvessels, but few adrenergic nerves were seen even after CS23 treatment. From these observations, basic fibroblast growth factor was suggested to promote the reinnervation of the newly formed microvessels.

Topics: Animals; Autonomic Nervous System; Calcitonin Gene-Related Peptide; Fibroblast Growth Factor 2; Male; Microcirculation; Nerve Regeneration; Rats; Rats, Wistar; Recombinant Proteins; Recurrence; Stomach; Stomach Ulcer; Vasoactive Intestinal Peptide

Accumulating evidence indicates that capsaicin-sensitive afferent fibers play a pivotal role in acute gastroprotection. However, whether they also influence healing of chronic gastric ulcers is still unknown. The effects of ablation of sensory neurons on acetic acid-induced chronic gastric ulcers in rats were investigated at morphologic and biochemical levels by computerized imaging analysis of the ulcerated area, histologic examination, and neuropeptide determination. Afferent nerve ablation, as a result of treating rats with a neurotoxic dose of capsaicin (50 + 50 mg/kg subcutaneously over 2 days), produced a significant increase in the ulcer area at 1 and 2 weeks after acetic acid injection. The delay in ulcer healing was associated with a marked and persistent decrease in tissue calcitonin gene-related peptide-like immunoreactivity, whereas gastric vasoactive intestinal polypeptide was unaffected by capsaicin pretreatment. Histologically, as compared with control rats, capsaicin-desensitized animals only differed in a slight increase in the inflammatory infiltrate during the early phase of ulcer formation. These findings suggest that capsaicin-sensitive afferent fibers may play a role in the healing of chronic experimental gastric ulcers in rats, but the underlying mechanisms remain to be elucidated and deserve further investigation.

Topics: Acetates; Acetic Acid; Animals; Calcitonin Gene-Related Peptide; Capsaicin; Chronic Disease; Male; Neurons, Afferent; Rats; Rats, Sprague-Dawley; Stomach Ulcer; Vasoactive Intestinal Peptide; Wound Healing

Neurochemical and functional studies were performed to investigate and to compare the effects of resiniferatoxin and capsaicin in the rat stomach. Neonatal administration of resiniferatoxin (0.6-1.6 mumol/kg subcutaneously (s.c.)) produced a marked decrease in gastric calcitonin gene-related peptide-like immunoreactivity in both secretory and non-secretory region of the stomach. Almost complete depletion of the peptide was determined by neonatal administration of capsaicin (164 mumol/kg s.c.). Vasoactive intestinal polypeptide-like immunoreactivity was concomitantly unaffected by resiniferatoxin or capsaicin, thus showing the selectivity of action of the neurotoxins on gastric afferent fibers. Oral administration of an equimolar dose (0.3 nmol/kg) of resiniferatoxin or capsaicin together with 50% ethanol reduced at a similar extent gastric haemorrhagic lesions produced by the mucosal barrier-breaker agent. These findings provide evidence that resiniferatoxin and capsaicin may act on a common neuronal target in the rat stomach and that the acute exciting (protective) effect is of the same magnitude.

Topics: Administration, Oral; Animals; Animals, Newborn; Calcitonin Gene-Related Peptide; Capsaicin; Diterpenes; Dose-Response Relationship, Drug; Ethanol; Gastric Mucosa; Gastrointestinal Hemorrhage; Injections, Subcutaneous; Male; Neurons, Afferent; Neurotoxins; Rats; Stomach Ulcer; Vasoactive Intestinal Peptide

The effects of water-immersion-induced stress and intraperitoneal (i.p.) administration of selected neuropeptides on the levels of thyrotropin-releasing hormone (TRH) and prostaglandin E2 (PGE2) were studied in the rat stomach. Water-immersion caused a significant decrease immunoreactive-TRH (ir-TRH) concentrations in the stomach, and a significant increase in ir-TRH concentrations in the gastric juice. The concentrations of PGE2 were significantly increased at 0.5-4 hrs, and significantly decreased at 6-8 hrs after water-immersion. In the experiment of i.p. administration of selected neuropeptides, the level of ir-TRH in the stomach was significantly decreased after VIP injection, whereas it was significantly increased after beta-endorphin injection. The concentration of PGE2 was significantly decreased in the stomach after i.p. administration of TRH and VIP. However, it did not change after beta-endorphin injection. These results indicate that some neuropeptides may participate in regulating the endogenous level of PGE2 and that these interrelations between neuropeptides and PGE2 may be important as ulcerogenic factors in stress ulcers induced by water-immersion in the rat.

Topics: Animals; beta-Endorphin; Dinoprostone; Gastric Juice; Gastric Mucosa; Immersion; Injections, Intraperitoneal; Male; Rats; Rats, Inbred Strains; Stomach Ulcer; Stress, Physiological; Thyrotropin-Releasing Hormone; Vasoactive Intestinal Peptide

In human antral membranes, VIP and its natural analogs inhibited the binding of HPLC-purified 125I-VIP, according to the following order of potency: VIP greater than rh GRF greater than helodermin greater than r PHI greater than PHM greater than p PHI greater than hp GRF greater than h, p secretin. No specific binding was detected in plasma membranes purified from the human fundus. In human antral membranes, Scatchard plots were compatible with the existence of two classes of VIP receptors, the first class with high affinity and low binding capacity (Kd = 0.1 nM, Bmax = 10 fmol/mg protein) and another class with a low affinity and higher binding capacity (Kd = 12) nM, Bmax = 1,000 fmol/mg protein). The structure of the VIP receptor in purified plasma membranes prepared from human antral glands and from the HGT-1 human gastric cancer cells was subsequently probed using the cross-linking reagent DSP and 125I-VIP. In agreement with the pharmacological study and the Scatchard analysis of the binding data, SDS gel electrophoresis of the solubilized receptor identified two radiolabeled peptides Mr 67,000 and 34,000 containing disulfide bonds. According to its sensitivity to low doses of VIP and to GTP, the Mr 67,000 binding site represents the membrane domains involved in the physiologial regulation of adenylate cyclase by VIP in normal and transformed human gastric epithelia.

Topics: Binding, Competitive; Cell Membrane; Gastrectomy; Gastric Mucosa; Humans; Kinetics; Pyloric Antrum; Receptors, Gastrointestinal Hormone; Receptors, Vasoactive Intestinal Peptide; Stomach Neoplasms; Stomach Ulcer; Vasoactive Intestinal Peptide