Rat Stomach Tissue Research Articles

Gastrin, Nitric Oxide Synthase and their Role in Ulceration and Distention of Stomach after Cisplatin and Taxol Treatment

Cisplatin, a potent broad spectrum anti-cancer agent, has been proven effective in the treatment of different kinds of cancer, such as bladder, lung, ovarian, head, neck, etc.. Drawbacks of this chemotherapeutic drug are its toxic side-effects, which include severe nausea, vomiting, stomach distention and peptic ulcer.Taxol is another effective chemotherapeutic agent which is usually used in conjection with cisplatin. It has demonstrated impressive activity in breast, ovarian, lung, and head and neck cancers. The toxic side-effects include nausea, vomiting, nephrotoxicity. The mechanism of these gastrointestinal side-effects are still unclear. Because of the role of NOS and gastrin on stomach smooth muscle contractility and gastroprotection, these were studied in the rats after cisplatin and taxol administration.Wistar rats(100-150 g) were injected with cisplatin(9 mg/kg) and taxol(20 mg/kg) in five divided dosages over a period of 5 days. Rats were killed one day after the last injection. Rat stomach tissues were fixed in Bouin’s solution and processed for light microscopy.

The influence of a novel pentadecapeptide, BPC 157, on NG-nitro- l-arginine methylester and l-arginine effects on stomach mucosa integrity and blood pressure

The known effects of a novel stomach pentadecapeptide BPC157 (10 μg or 10 ng/kg), namely its salutary activity against ethanol (96%, i.g.)-induced gastric lesions (simultaneously applied i.p.) and in blood pressure maintenance (given i.v.), were investigated in rats challenged with a combination of N G-nitro- l-arginine methylester ( l-NAME) (5 mg/kg i.v.), a competitive inhibitor of endothelium nitric oxide (NO)-generation and NO precursor, l-arginine (200 mg/kg i.v.) ( d-arginine was ineffective). In the gastric lesions assay, NO agents were given 5 min before ethanol injury and BPC 157 medication. Given alone, BPC157 had an antiulcer effect, as did l-arginine, but l-NAME had no effect. l-NAME completely abolished the effect of l-arginine, whereas it only attenuated the effect of BPC 157. After application of the combination of l-NAME+ l-arginine, the BPC157 effect was additionally impaired. In blood pressure studies, compared with l-arginine, pentadecapeptide BPC 157 (without effect on basal normal values) had both a mimicking effect (impaired l-NAME-blood pressure increase, when applied prophylactically and decreased already raised l-NAME values, given at the time of the maximal l-NAME-blood pressure increase (i.e., 10 min after l-NAME)) and preventive activity ( l-arginine-induced moderate blood pressure decrease was prevented by BPC 157 pretreatment). When BPC 157 was given 10 min after l-NAME+ l-arginine combination, which still led to a blood pressure increase, its previously clear effect (noted in l-NAME treated rats) disappeared. In vitro, in gastric mucosa from rat stomach tissue homogenates, BPC 157, given in the same dose (100 μM) as l-arginine, induced a comparable generation of NO. But, BPC 157 effect could not be inhibited by l-NAME, even when l-NAME was given in a tenfold (100 versus 1000 μM) higher dose than that needed for inhibition of the l-arginine effect. NO synthesis was blunted when the pentadecapeptide BPC 157 and l-arginine were combined. In summary, BPC 157 could interfere with the effects of NO on both gastric mucosal integrity and blood pressure maintenance in a specific way, especially with l-arginine, having a more prominent and/or particularly different effect from that of NO.

Molecular cloning and expression of a cDNA encoding the secretin receptor.

Secretin is a 27 amino acid peptide which stimulates the secretion of bicarbonate, enzymes and potassium ion from the pancreas. A complementary DNA encoding the rat secretin receptor was isolated from a CDM8 expression library of NG108-15 cell line. The secretin receptor expressed in COS cells could specifically bind the iodinated secretin with high and low affinities. Co-expression of the secretin receptor with the alpha-subunit of rat Gs protein increased the concentration of the high affinity receptor in the membrane fraction of the transfected COS cells. Secretin could stimulate accumulation of cAMP in COS cells expressing the cloned secretin receptor. The nucleotide sequence analysis of the cDNA has revealed that the secretin receptor consists of 449 amino acids with a calculated Mr of 48,696. The secretin receptor contains seven putative transmembrane segments, and belongs to a family of the G protein-coupled receptor. However, the amino acid sequence of the secretin receptor has no significant similarity with that of other G protein-coupled receptors. A 2.5 kb mRNA coding for the secretin receptor could be detected in NG108-15 cells, and rat heart, stomach and pancreatic tissue.

Rapid Microdetermination of Hydroxyproline in Biomedical Samples by Flow Injection Analysis Using Cysteine as an Antioxidant

A new practical method for the rapid microdetermination of hydroxyproline (Hyp) in biomedical samples, such as tissue and urine, in the presence of a definite amount of cysteine as antioxidant was established by means of the modified KISO method using flow injection analysis. This method uses no organic solvent and requires only 9 min for each sample, which can be injected every 3 min (about 5 h is sufficient for 100 samples). A good linear relationship (r=0.99996) was obtained between the concentration of Hyp (0–80μg/ml) and the absorbance (0–0.514). In biomedical samples (hydrolyzates of rat stomach tissue), the recoveries (94.8–103.7%) and the reproducibility (the mean of RSD; 0.484% for ten kinds of rat tissues) were satisfactory. The correlation between values from this method and from the conventional KISO method was shown to be good enough (r=0.966) for hydrolyzate samples (N=95), when a proper amount of cysteine solution was added to both the sample and standard solutions and the concentration of the oxidant was optimized to Hyp contents.

Phospholipase inhibition and prostacyclin generation by gastric muscularis and mucosa layers.

The effects of drugs which interfere with arachidonate metabolism as well as glucocorticoid-induced anti-phospholipase proteins (APP) have been studied on PGI2 generation by rat stomach tissue. Indomethacin inhibited PGI2 generation both in vitro and ex vivo while dexamethasone was ineffective in both instances. APP inhibited PGI2 generation in vitro. The results are discussed in the light of the possible mode of action of glucocorticoids. Prostacyclin (PGI2) is the major cyclo oxygenase metabolite in the rat gastric mucosa and exerts gastroprotective actions. Therefore a correlation between the inhibition of PGI2 synthesis and the induction of gastric damage has been suggested for the non-steroidal anti-inflammatory drugs. Glucocorticoids inhibit phospholipase A2 (PLA2) by inducing in the target cells the synthesis of inhibitory proteins, the lipocortins, and consequently reduce the release of eicosanoids in a number of cells and tissues. However, there is a surprising paucity of information on the effect of glucocorticoids on arachidonic acid (AA) metabolism in the gastro-intestinal tract. Moreover, the relationship between steroid administration and gastric damage is still controversial. The present work was undertaken to investigate the effect of drugs which interfere with AA metabolism on the synthesis of PGI2 by rat stomach mucosa and by the underlying muscularis layer both in vitro and ex vivo.

Comparison of Kinins Derived from Rat Stomach Tissue and Produced by Catheptic Enzyme in Rat Stomach

Four uterine-contractile substances (a, b, c and d) and three uterine-contractile substances (a′, c′ and d′) were obtained from the reaction mixture of rat plasma kininogen with the kinin-forming enzyme in rat stomach and the homogenate of the rat stomach with 0.2% acetic acid, respectively. By high performance liquid chromatography with a Zorbax ODS reversed-phase column, the retention times of materials a, c and d were found to be equal to those of materials a′, c′ and d′, and they were not equal to those of kallidin, methionyl-lysyl-bradykinin (MLBK) and bradykinin (BK). The retention time of material b was equal to that of BK. The uterine-contractile activities of the materials a, b, c, d, a′, c′ and d′ were all abolished by chymotrypsin, but not by trypsin treatment. These materials all relaxed the isolated rat duodenum in the presence of atropine, dibenamine, diphenhydramine and propranolol, and they produced a fall in rabbit blood pressure after administration of atropine, dibenamine and propranolol. The content ratios of a: b: c: d and a′: c′: d′ were 4: 4: 67: 25 and 65: 19: 16, respectively, as calculated from the uterine-contractile activities of these materials.

Concentration of biogenic amines in stomach tissues of rats with reduced gastric circulation

Concentration of biogenic amines in stomach tissues of rats with reduced gastric circulation

Elevated levels of smooth muscle autoantibodies in patients with acromegaly.

Screening of sera from patients with central nervous system (CNS) tumors for serum antibodies to tumor and normal tissue antigens revealed that the sera from a significant percentage of patients with pituitary adenoma demonstrated reactivity for smooth muscle antibodies (SMA) at a serum titer (1/25) at which other CNS tumors are devoid of this reaction. The sera were assessed by an indirect immunofluorescent antibody assay on fresh cryostat sections of rat kidney, liver, diaphragm, and stomach tissue. Absorption of SMA-positive sera with extracts containing smooth muscle tissue abolished the reaction. The overall incidence of SMA among patients harboring pituitary tumors was 30% (12/40). Assessment of the functional types of the tumor revealed a distinct predilection for such findings among patients with clinical acromegaly. Among patients with hypersecretion of growth hormone (CA) 90% (9/10) have SMA (both IgG and IgM type) whereas SMA was positive in only 10% (3/30) of corresponding group of patients with pituitary tumors resulting in hypercortisolemia or those that did not result in a hyperfunctional endocrine state.

Changes in the nucleic acid and cyclic AMP content in neurogenic dystrophies of the stomach

A decrease in the RNA content was found in the stomach tissue of rats following degenerative changes in the organ induced by injury to the duodenum. A sharp fall in the cyclic AMP level in the gastric mucosa of rabbits was found under the same experimental conditions. The role of these changes in the mechanism of development of destructive and metabolic disturbances during the formation of neurogenic dystrophies caused by extraordinary stimulation is analyzed.

Histidine decarboxylase of rat stomach and other mammalian tissues.

With minute quantities of C14 l-histidine as substrate, rat stomach histidine decarboxylase shows a far higher activity than that from any other mammalian organ tested. Its maximum activity is ph 7.2. The maximum activity of rabbit kidney histidine decarboxylase is 8.0. Although the activity of the latter is greatly enhanced by benzene, rat stomach histidine decarboxylase activity is strongly inhibited by benzene. It is concluded that there are at least two mammalian enzymes with the same specificity which have major differences in molecular configuration. Studies of some properties of histidine decarboxylase are presented. Histidine decarboxylase activity of rat stomach drops markedly as early as 1 day following hypophysectomy. No comparable drop follows adrenalectomy.