Cellular Energetical Actions of "Chemical" and "Surgical" Vagotomy in Gastrointestinal Mucosal Damage and Protection: Similarities, Differences and Significance for Brain-Gut Function (original) (raw)
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Vagal nerve and the gastric mucosal defense
Journal of Physiology-Paris, 1993
An essential role for an intact vagal nerve has been proven in the development of gastric mucosal cyto-and general protection. On the other hand, chemically-induced (ethanol, HC1, indomethacin) gastric mucosal damage is enhanced after acute surgical vagotomy. The aims of this paper were to study the possible mechanisms of the vagal nerve in the development of gastric mucosal defense. The following questions were addressed: l) effect of surgical vagotomy on the development of ethanol-(ETOH). HCI-. and indomethacin (IND)-induced gastric mucosal damage: 2) changes in the gastric mucosal defense by scavengers, prostacyclin and other compounds (small doses of atropine and cimetidine: 3) changes in the gastric mucosal vascular permeability due to chemicals: 4) effect of indomethacin in the ETOH and HCI models with and without surgical vagotomy; 5) changes in the gastric mucosal content of prostacyclin and PGE2 in the ETOH and HCI models after surgical vagotomy: and 6) changes in the role of SH-groups in gastric mucosal defense after surgical vagotomy. It was found that: l) the gastric mucosal damage produced by chemicals (ETOH. HCI, and indomethacin) was enhanced after surgical vagotomy; 2) the cyto-and general gastric protective effects of 15-carotene, prostacyclin, and small doses of atropine and cimetidine disappeared after surgical vagotomy: 3) the vascular permeability due to chemicals (E'IOH. HCI, indomethacin) significantly increased after surgical vagotomy in association with an increase in both number and severity of gastric mucosal lesions: 4) IND alone (in animals with an intact vagus) did not produce gastric mucosal lesions (in l-h experiments), but it aggravated ETOH-induced gastric mucosal damage (both its number and severity); 5) the gastric mucosal levels of prostacyclin and PGE_~ decreased after surgical vagotomy: 6) IND application (after surgical vagotomy) decreased further the tissue levels of prostacyclin and PGE2 in association with an increase of gastric mucosal damage: and 7) the gastric mucosal protective effects of SH-groups were abolished by surgical vagotomy. gastric mucosal damage / acute surgical vagotomy / cytoproteetion / SH-groups / vascular permeability
Membrane-bound Atp-dependent Energy Systems and the Gastrointestinal Mucosal Damage and Protection, 2016
The peak of the membrane ATPase appears earlier than the gastric hypersecretion (Figure 73). When we prepared the membrane ATPase from the forestomach (rumen), we also found its peak earlier than the ulcer development (Shay et al., 1945) (Figure 74). It is interesting to note that the changes in the membrane ATPase reached its peak at the same time in both stomach parts after pylorus-ligation (4 hours after the pyloric ligation). When we compared the sequence of biochemistry, gastric hypersecretion and ulcer development, we found a similar sequence to that in patients with antral, duodenal and jejunal ulcers. The membrane ATPase can be specifically inhibited by ouabain application. This principal argument offers an approach to the changes in the gastric acid output and concentration) and ulcer development (Figures 75, 76). The tissue level of cAMP decreased significantly in both parts of the rat stomach (Mózsik et al., 1978 a, c; Mózsik et al., 1979 a, b, c, d, e, f). 8.1.2. 24-hour pylorus-ligated rats after bilateral surgical vagotomy After a 24-hour bilateral surgical vagotomy, the gastric acid secretory responses and gastric ulcer significantly decreased (Table 38), meanwhile the ATP-ADP transformation significantly decreased in both glandular part and the forestomach (Figures 77, 78).
Inflammopharmacology, 1999
Background. Indomethacin (IND) is a widely used non-steroidal anti-inflammatory agent in the treatment of various inflammatory disorders, which causes gastrointestinal injury in humans and animal experiments. Vitamin A and/3-carotene prevent the IND-induced gastric mucosal injury. These compounds modify the membrane-bound ATP-dependent energy systems. The aims of this investigation were: (1) To study the IND-induced gastric mucosal damage and its prevention by vitamin A and/3-carotene; (2) to measure the biochemical compounds of the gastric mucosa {ATE ADP, ATP / ADP, AMP, ATP + ADP + AMP, ' energy charge' (ATP § 0.5 ADP) / (ATP + ADP + AMP), cAMP, lactate} under the circumstances mentioned above; (3) to analyze the extra-and intracellular regulatory mechanisms between the membrane-bound ATP-dependent energy systems. Methods. The observations were carried out with CFY (Sprague-Dawstrein rats, weighing 180-210 g). The gastric mucosal damage was produced by IND (20 mg/kg sc. administration) and it was prevented by vitamin A (or r-carotene), given in doses of 0.01-0.1 to 1.0-10.0 mg/kg ig. Different biochemical compounds (ATE ADP, AMP, cAMP, lactate) and parameters (ATP/ADP, adenylate pool, 'energy charge') were measured and calculated. Results. (1) Vitamin A and r-carotene prevented dose-dependently the 1ND-induced gastric mucosal damage; (2) the extent of ATP-ADP transformation was increased significantly, while the ATP-cAMP decreased in the gastric mucosa after IND-treatment; (3) vitamin A and /3carotene enhanced the extent of ATP-cAMP transformation, while the ATP-ADP transformation was inhibited (the actions were dose-dependent responses); (4) No change was found in 'energy charge' by IND, while its value decreased significantly with vitamin A and r-carotene. Conclusions. (1) A very complex extra-and intracellular feedback mechanism system exists in the gastric mucosa during IND, IND § vitamin A, and IND § r-carotene treatments; (2) The gastric mucosal preventive effect of vitamin A and r-carotene only partly depend on their scavenger properties.
Journal of Physiology-Paris, 1993
The biochemical background of ethanol-(ETOH) induced gastric mucosal damage was studied in rats with intact vagus and after acute surgical vagotomy. Observations were carried out on Sprague-Dawley (CFY) strain rats of both sexes. Gastric mucosal lesions were produced by intragastric administration of I ml 96% ethanol. Bilateral truncal surgical vagotomy was carried out 30 min before ETOH administration. The number and severity of gastric mucosal lesions was noted 1 h after ETOH administration. Biochemical measurements (gastric mucosal level of ATP. ADP. AMP. cAMP and lactate) were carried out from the total homogenized gastric mucosa. The adenylate pool (ATP + ADP + AMP). energy charge ((ATP + 0.5 ADP)/(ATP + ADP + AMP)) and ratio of ATP/ADP were calculated. It was found that: 1) ATP transformation into ADP increased, while ATP transformation in cAMP decreased in ethanol-treated animals with intact vagus nerve, while these transformations were quite the opposite in vagotomized animals: 2) no significant changes were found in the tissue level of lactate: and 3) the extent of biochemical changes was significantly less after surgical vagotomy. It is concluded that an intact vagus is basically necessary for the metabolic adaptation of gastric mucosa.
Regulatory mechanism of acid secretion in the damaged stomach: Role of endogenous nitric oxide
Journal of Gastroenterology and Hepatology, 2000
15 (Suppl.) D37-D45 protect the stomach against subsequent challenge with necrotizing agents. Previous studies have shown that the gastric alkaline response incurred in the rat stomach after damage with hypertonic solution results from both the inhibition of acid secretion caused by the release of endogenous prostaglandins (PG) and the increased level of HCO 3 and that these factors play a role in the functional and morphological NITRIC OXIDE, HELICOBACTER PYLORI AND GASTROINTESTINAL DISORDERS Abstract The present article overviews the regulatory mechanism of acid secretion in the stomach after damage with taurocholate (TC), one of the bile acids. Mucosal exposure of a rat stomach to 20 mmol/L TC for 30 min caused a decrease of acid secretion with a concomitant increase in nitric oxide (NO) and prostaglandin (PG) E 2 (PGE 2 ) as well as Ca 2+ in the luminal contents. Prior administration of N G -nitro-L-arginine methyl ester (L-NAME), as well as indomethacin, significantly attenuated the reduction of acid secretion by TC and acid secretion was even increased in the presence of L-NAME. The acid stimulatory effect of L-NAME in the damaged stomach was not mimicked by aminoguanidine and was antagonized by co-administration of L-arginine but not D-arginine. Increased NO release in the damaged stomach was suppressed by pretreatment with L-NAME or co-application of EGTA and the latter also inhibited the increase in luminal Ca 2+ . The enhanced acid secretory response in the presence of L-NAME was also inhibited by cimetidine, FPL-52694 (a mast cell stabilizer) or sensory deafferentation. Mucosal exposure to TC caused an increase in luminal histamine output, together with a decrease in the number of mucosal mast cells in the stomach. These changes were prevented by FPL-52694 and sensory deafferentation and were also partly suppressed by indomethacin. In addition, the acid stimulatory action of L-NAME in the damaged stomach was significantly mitigated when indomethacin was administered together with L-NAME. We conclude that: (i) damage in the stomach may activate acid a stimulatory pathway in addition to a PG-, NO-and Ca 2+ -dependent inhibitory mechanism, but the latter effect overcomes the former, resulting in a decrease in acid secretion; (ii) acid stimulation in the damaged stomach is mediated by histamine released from the mucosal mast cell, a process interacting with capsaicin-sensitive sensory nerves; (iii) the increase in luminal Ca 2+ plays a role in increasing NO production and, hence, in regulating acid secretion; and (iv) PG may have a dual role in the regulation of acid secretion in the damaged stomach: an inhibitory effect at the parietal cell and an excitatory effect, probably through enhancing the release of mucosal histamine.
Adverse effects of vagotomy on ethanol-induced gastric injury in the rat
Digestive Diseases and Sciences, 1993
Truncal vagotomy is known to aggravate the damaging effects of alcohol-induced gastric injury and prevent the occurrence of adaptive cytoprotection against such injury by a mild irritant. This study was undertaken to determine whether aberrations in glutathione (GSH) metabolism were responsible for these vagotomy-induced effects, Fasted rats (6-8~group) were subjected to truncal vagotomy and pyloroplasty or sham vagotomy and pyloroplasty. One week later they were given 2 ml of oral saline or the mild irritant, 25% ethanol (EtOH). Thirty minutes following such treatment, animals were either sacrificed or orally received 2 ml of 100% EtOH and then were sacrificed 5 min later. At sacrifice, in each experimental group, stomachs were removed and either evaluated macroseopicalty for the degree of injury involving the glandular gastric epithelium or samples of the mucosa were prepared for measurement of total GSH levels or GSH peroxidase (GPX) and GSH reductase (GRT) activity. In nonvagotomized animals, saline treatment prior to 100% EtOH exposure resulted in injury to the glandular epithelium involving approximately 18%. Treatment with 25% EtOH prior to 100% EtOH exposure virtually abolished this injury. In vagotomized animals, 100% EtOH elicited almost three times the amount of injury observed in the nonvagotomized state and the protective effect of 25% EtOH pretreatment was prevented. Effects of the various treatment modalities on GPX and GRT activity were not significantly different from control values. When mucosal GSH results were plotted against the presence or absence of gastric injury among the various groups studied, no significant correlation was apparent. Thus, aberrations in glutathione metabolism do not explain the absence of adaptive cytoprotection following vagotomY or the exacerbation of alcohoLinduced damage under conditions of vagal denervation.
Role of brain-gut axis in healing of gastric ulcers
Journal of physiology and pharmacology: an official journal of the Polish Physiological Society
The previous studies demonstrated the pivotal role of capsaicin-sensitive peptidergic sensory neurons and vagal nerves in the maintenance of gastric mucosal integrity. The aim of the present study was: 1). to examine the effect of the functional ablation of sensory neurons with neurotoxic dose of capsaicin and surgical vagotomy on the course of healing of gastric ulcer in rat, and 2). to compare the ulcer healing action of leptin in rats with or without capsaicin-induced inactivation of sensory neurons. Three series of experiments (A, B and C) were performed in Wistar rats with gastric ulcers induced by acetic acid method. In series A, the course of ulcer healing was compared in rats with intact and capsaicin-inactivated sensory neurons. In the series B, the effect of vagotomy on the ulcer healing and accompanying changes in GBF were determined at day 8 and 16 after ulcer induction. The rats of series C, consisting of animals with intact nerves or those with capsaicin-denervation, r...
Cellular mechanisms of β-carotene-induced gastric cytoprotection in indomethacin-treated rats
InflammoPharmacology, 1998
Cellular mechanisms of p-carotene-induced gastric cytoprotection in indomethacin-treated rats. lnflammopharmacology. 1998:6:27 40. lndomethacin (IND) is a non-steroidal anti-inflammatory agent which is widely used in the treatment of various inflammatory disorders. The drug causes gastrointestinal injury in humans and experimental animals. The aim of these studies was to examine the time course correlation between the macroscopic appearance of mucosal damage, tissue level of PGE2 and adenosine nucleotide metabolism during the development of indomethacin (IND)-induced mucosal damage and its prevention by 13-carotene. The observations were carried out on both sexes of CFY-strain rats, weighing 180-200 g. Gastric mucosal damage was produced by subcutaneous administration of IND (20 mg/kg). [3-Carotene (Hoffman-La Roche, Switzerland) was given intragastrically at the time of IND administration at doses of 0.01, 0.1, 1 and 10 mg/kg. The animals were sacrificed at 0, 1, 2, 3 and 4 h after 1ND administration when the number and severity of mucosal lesions were noted and the tissue levels of ATP, ADP, AMP. cAMP`, lactate and PGE2 were measured from the total homogenate of gastric mucosa. The ratio of ADP/ATE the values of the adenylate pool (ATP+ADP+AMP), and 'energy charge' [(ATP+0.SADP) / (ATP+ADP+AM P)] were calculated. It was found that: (a) gastric mucosal lesions appear macroscopically 2 h after 1N D administration; (b) the tissue level of ATP decreased, while ADP was increased 1 h after administration; (c) the most significant decrease in cAMP was found 1 h after IND administration, and thereafter its level returned to baseline; (d) 13-carotene dose-dependently prevented the IND-induced mucosal damage and elevated the cAMP level, but it did not alter the mucosal PGE2 level 3 or 4 h after IND administration; (e) [3carotene produced an elevation in ATP and a decrease in ADP level; (f) no significant changes were found in 'energy charge" of the gastric mucosa in IND-treated animals. The development of gastric mucosal damage due to IND was associated with increased energy liberation, i.e. transformation of ATP into ADP, and decreased ATP cAMP transformation. The significant decrease in cAMP preceded the macroscopic appearance of mucosal damage. The increase in ATP cAMP transformation is involved in the development of [3-carotene-induced gastric cytoprotection.
Annals of surgery, 1976
In 9 normal and 42 duodenal ulcer patients, acid and gastrin studies were performed. Basal, Oxo and Histalog stimulated acid secretion was conducted on each patient. In 24 patients post vagotomy pyloroplasty or vagotomy antrectomy, these studies were repeated within three months after surgery. Two groups of duodenal ulcer patients were identified; those who did respond and those who did not respond to Oxo stimulation. In the "responders," Oxo stimulated acid output and gastrin secretion increased significantly over basal values. Both vagotomy pyloroplasty and vagotomy antrectomy caused a similar significant decrease in Oxo and Histalog stimulated acid output. In two patients with incomplete vagotomy, antrectomy, but not pyloroplasty abolished the Oxo stimulated acid response. These data suggest that OXO stimulation test can select patients with a significant antral component in whom vagotomy and antrectomy would be the appropriate procedure. Our results also indicate that ...