Pepsin In Rats Research Articles

Herba Swertiae Benefits the Gastrointestinal System In Vivo

Due to the increasing usage of herbal medicines and natural products for the body function management and ailments treatment and the lack of study on the beneficial effect of Herba Swertiae, a widely used traditional herbal medicine, this paper aimed to investigate the effect of Herba Swertiae on gastrointestinal system in vivo. The effect of Herba Swertiae on gastric emptying and intestinal propulsion was examined in mice; the effect of Herba Swertiae on gastric acid secretion and pepsin activity was tested in rats; and the effect of Herba Swertiae on the mobility of ileum was evaluated by ex vivo experiments using isolated ileum from guinea pig. The results showed that Herba Swertiae markedly enhanced gastric emptying and intestinal propulsion in mice. Also, Herba Swertiae remarkably increased the gastric acid secretion, the acidity of gastric acid, and the activity of pepsin in rats. Of note, these effects were comparable to that of positive control. Moreover, Herba Swertiae exerted a potent promoting effect on the mobility of ileum of guinea pigs, with a marked increase in the muscular tension force and contraction amplitude in the isolated ileum. Moreover, Herba Swertiae excited the isolated ileum that was inhibited by atropine. Taken together, Herba Swertiae exerts markable beneficial effects on gastrointestinal system in vivo. More studies are warranted for the investigation of the underlying mechanisms for its beneficial effects.

Application of heptapeptides containing D‐amino acid residues immobilized to magnetic particles and Sepharose for the study of binding properties of gastric aspartic proteases

Synthetic heptapeptides containing D-amino acid residues and differing in the content of L-phenylalanine and L-tyrosine residues and their position (Val-D-Leu-Pro-Tyr-Phe-Val-D-Leu, Val-D-Leu-Pro-Tyr-Tyr-Val-D-Leu, Val-D-Leu-Pro-Phe-Tyr-Val-D-Leu) were immobilized to two types of carriers: glyoxal-activated magnetic agarose particles and CNBr-activated Sepharose. In both cases, peptides were immobilized via their terminal amino group. Immobilized peptides were used for the study of binding properties of two gastric aspartic proteases (porcine pepsin A and rat pepsin C). Porcine pepsin A was adsorbed to all studied peptide-modified magnetic carriers, while rat pepsin C interacted with immobilized ligands only slightly. Similar results were obtained in affinity chromatographic experiments using heptapeptides immobilized to Sepharose.

Experimental model of smoking and simulation of reflux with acid and pepsin in rats

PURPOSE: To develop experimental models to evaluate the effects of hydrochloric acid associated with the pepsin instilled in the mucosa of the upper esophagus and the esophagogastric junction of young male rats Wistar, simulating injury caused by gastroesophageal reflux on the mucosa of aero-digestive tract in humans as well as the action of the risk exposure of mucosa to cigarette smoke. METHODS: Fifty young male Wistar rats divided in 5 groups with 10 animals each one, respectively simulating pharyngo-laryngeal reflux and gastroesophageal reflux, pharyngo-laryngeal reflux and smoking, smoking only, gastroesophageal reflux and control group. RESULTS: The histopathologic studies no recorded neoplasias, only mild changes and no significant alterations. The hemo-oximetry (carboxyhemoglobin and methemoglobim) and CO2 concentration confirm that the animals were submitted to high intensity of exposure to carcinogens in tobacco and its derivatives. CONCLUSION: The experimental models were highly efficient, practical, easy to use and economical and can be employed in other similar studies to determine the harmful effects by smoking and reflux.

Peptide inhibitor modified magnetic particles for pepsin separation

Synthetic heptapeptide containing D-amino acid residues (Val-D-Leu-Pro-Phe-Phe-Val-D-Leu) was coupled to glyoxal-activated magnetic agarose particles via the free peptide amino group. The peptide-modified magnetic particles were used for the separation of pepsins. Porcine pepsin A and human pepsin A were adsorbed to the magnetic peptide-modified affinity carrier, while the rat pepsin C and human pepsin C did not interact with the immobilized ligand. Conditions of pepsin adsorption to peptide-modified magnetic particles, as well as elution buffers were optimized. Porcine pepsin A did not interact with the immobilized peptide in the presence of pepsin inhibitor pepstatin A, indicating that the enzyme binding site is involved in the studied interaction. The elaborated method represents a rapid and simple technique not only for the separation of pepsins but also, in combination with MS, for the enzyme detection and determination.

Effect of rotating electromagnetic fields on proteolytic activity of pepsin in rats.

We studied the effect of 37-GHz electromagnetic field on proteolytic activity of pepsin in Wistar rats. The plane of polarization of the electromagnetic fields rotated in either right-handed or left-handed sense (D- and L-chirality). D-Polarization stimulated, while L-polarization suppressed pepsin production.

Effect of Tityus serrulatus scorpion toxin on serum gastrin levels in anaesthetized rat

Scorpion toxin induces gastric secretion of acid and pepsin in rats. These effects seem to be mediated by the release of acetylcholine and histamine. However, the role of gastrin in the scorpion-toxin-induced gastric secretion is unknown. We describe the effects of the T 1 fraction purified from Tityus serrulatus scorpion venom on serum and on antral tissue gastrin levels in anaesthetized rats. Gastrin levels in serum and in the antral mucosa were measured before and at intervals 5, 15, 30, 60, 90 up to 120 min after the intravenous injection of saline or the T 1 fraction of scorpion venom (0.25 mg/kg) into anaesthetized rats. Antral G-cells were submitted to immunocytochemistry and electron microscopy. The data on gastrin were correlated with the gastric juice volume, and the acid and pepsin output increases induced by toxin. Scorpion toxin induced a significant increase in volume, acid output and pepsin output of gastric juice and gastrin serum levels 15–60 min after injection. Simultaneous measurements of antral gastrin levels did not show significant effects. The number of dense, intermediate and empty granules per μm 2 in the cytoplasm of antral G-cells was not significantly changed 60 min after saline or toxin injection. Scorpion toxin significantly increased serum gastrin; levels in rats.

Fasting increases the expression of basic fibroblast growth factor (FGF-2) messenger ribonucleic acid in rat hypothalamus.

Basic fibroblast growth factor (FGF-2) has been isolated from the brain, but the regulation of FGF-2 synthesis in the brain is not yet fully understood. Since exogenously administered FGF-2 has been reported to suppress food intake as well as the secretion of gastric acid and pepsin in rats, we examined the effect of fasting on FGF-2 mRNA levels in the hypothalamus and the cerebral cortex of male rats, using RNase protection assay. Fasting for 72 h resulted in an approximately 2-fold increase in FGF-2 mRNA level in the hypothalamus but did not affect FGF-2 mRNA level in the cerebral cortex significantly. These findings support the hypothesis that FGF-2 plays a significant role in regulation of hypothalamic function.

A tonic inhibitory control of rat pepsin secretion is mediated by central GABA-A receptors

Polidori, C., I. Panocka, R. Ciccocioppo, M. Broccardo, G. Improta, D. Regoli and M. Massi. Further evidence that the tachykinin Pg-Kii is a potent agonist at central Nk-3, but not Nk-1, receptors. Peptides 18(6) 825–833, 1997.—Intracerebroventricular (ICV) injection of tachykinins (TKs) inhibits ethanol intake and angiotensin II-induced water intake; the effects are apparently mediated by NK-3 and NK-1 receptors, respectively. The present study evaluated the effect of the TK PG-KII, a novel kassinin-like peptide isolated from the skin of the Australian frog Pseudophryne güntheri, in these in vivo tests for central activity. PG-KII, given by ICV injection, potently inhibited alcohol intake in genetically selected alcohol-preferring rats, being about 3 times more potent than the selective NK-3 receptor agonist NH2-SENK. The dose of 100 ng/rat, that markedly inhibited ethanol intake, did not inhibit food intake and prandial drinking in food deprived rats, providing evidence that the effect of PG-KII on ethanol intake is behaviorally selective. The effect on ethanol intake was inhibited by ICV injection of the NK-3 receptor antagonist R820, but was not modified by the NK-1 receptor antagonist SR 140333. PG-KII inhibited drinking induced by angiotensin II only at doses of 300 or 1000 ng/rat, being about 5 times less potent than the selective NK-1 receptor agonist [Sar9,Met(O2)11]substance P. These doses of PG-KII produced also marked increase in competing behaviors, such as grooming and locomotion. The dose of 1000 ng/rat evoked a general inhibition of the ingestive behavior, reducing also food intake. The ICV injection of the NK-1 receptor antagonist SR 140333 only slightly inhibited the effect of PG-KII on angiotensin II-induced drinking, while it markedly reduced that of [Sar9,Met(O2)11]substance P. These findings, in accordance with those of previous studies, indicate that PG-KII is endowed with marked activity at central NK-3 receptors, and low activity at NK-1 receptors.

Evidence that gastric antisecretory action of lipopolysaccharide is not due to a toxic effect on gastric parietal cells.

We have recently found that bacterial lipopolysaccharide (LPS) or endotoxin at minute doses inhibits the secretion of gastric acid and pepsin in rats. The present study was performed to determine whether this antisecretory action of LPS was a reversible biological response or a result of the destruction of gastric parietal cells by endotoxin. The intraperitoneal injection of LPS into pylorus-ligated rats resulted in a dose-related (40-4000 ng/kg) decrease in gastric acid secretion, with maximal inhibition being observed at a dose of 4000 ng/kg. The stomach then was examined both macroscopically and microscopically for the presence or absence of mucosal lesions or damaged gastric parietal cells. No morphological changes in the gastric mucosal structure including parietal cells were observed even in the rats injected with 4000 ng/kg of LPS. Next, basal gastric acid output was compared in the rats that had received LPS (4000 ng/kg, intraperitoneal) or saline alone 24 hr before. There was no significant difference in gastric acid secretion between the saline- and LPS-pretreated groups, indicating that the secretory capacity of gastric parietal cells returned to the control level at 24 hr after the injection of a maximal antisecretory dose of LPS. These results clearly suggest that the LPS-induced inhibition of gastric secretion results not from its toxic or destructive effect on the gastric secretory mechanism but from its reversible biological effect on gastric physiology.

The gastric antisecretory action of lipopolysaccharide is blocked by indomethacin

We have recently found that bacterial lipopolysaccharide (LPS) at minute doses inhibits the secretion of gastric acid and pepsin in rats. The present study was performed to examine the mechanism by which LPS exerts its antisecretory action. The i.p. injection of LPS resulted in a dose-dependent (40–4000 ng/kg) decrease in gastric acid output in pylorus-ligated rats. However, preinjection of indomethacin (2–10 mg/kg s.c.), an inhibitor of prostaglandin biosynthesis, prevented the LPS-induced inhibition of gastric secretion in a dose-related manner, while these concentrations of indomethacin by themselves did not affect gastric acid output. These results suggest that LPS requires an intact prostaglandin system to exhibit action on gastric secretion.

The N-terminal sequence of rat pepsinogen

The amino-acid sequence of 96 residues in the N-terminal region of rat pepsinogen I was determined and the first 46 residues were found to constitute the activation peptide segment. There was high degree of homology between the activation segments of rat pepsinogen and some pepsinogens A (pig, cow, Japanese monkey and human). However, the number of residues substituted between rat and the other pepsinogens were considerably larger than those among pepsinogens A. In the N-terminal 24 residues of active pepsin, homology (88%) between rat pepsin and human gastricsin was higher than that (50%) between rat pepsin and pepsin A from human or pig. This strongly suggests that rat pepsin should be classified as pepsin C.

Exogenous and endogenous acid and pepsins in the pathogenesis of duodenal ulcers in the rat.

A continuous subcutaneous infusion for 24 hr of the gastric secretagogues, pentagastrin (4 micrograms/kg/min) together with carbachol (0.8 micrograms/kg/min) produced a 100% incidence of duodenal ulcers (DU) in male albino Wistar rats. The mean acid output producing these duodenal ulcers was 2.3 mmol/24 hr, with a gastric secretory volume of 25 (+/- 1) ml/24 hr at an acid concentration of 91 (+/- 2) mmol/liter. The pepsin activity in the gastric juice was 185 micrograms/ml. To simulate this acid-pepsin hypersecretion, acid and/or pepsin was infused intragastrically for 24 hr. The intragastric infusion of hydrochloric acid (0.1 M, 0.2 M, 0.5 M) alone and hog purified pepsin (2.5, 5, 10 mg/24 hr) at a constant rate of 1 ml/hr for 24 hr failed to produce duodenal ulcers in rats although gastric lesions in the body of the stomach were produced. The infusion of 0.2 M HCl with 5 mg pepsin over 24 hr produced DU in two of 10 rats. However, pooled secretagogue-stimulated gastric juice, infused intragastrically, produced DUs in 11 of 12 rats. Acid alone does not produce DU experimentally in rats at the rate of infusion used in these experiments. Acid and exogenous procine pepsin (similar to human pepsin 3 on agar gel electrophoresis) rarely produced duodenal ulcers. However, acid and endogenous rat pepsin are needed together for the duodenal ulcerogenesis. This pepsin may be an obligatory ulcerogenic factor in the rat.