Somatostatin receptors in the gastrointestinal tract in health and disease.

The multiple actions of somatostatin are mediated by specific membrane-bound receptors present in all somatostatin target tissues, such as brain, pituitary, pancreas, and gastrointestinal tract. Three different types of tissues in the human gastrointestinal tract express somatostatin receptors: (1) the gastrointestinal mucosa, (2) the peripheral nervous system, and (3) the gut-associated lymphoid tissue, where the receptors are preferentially located in germinal centers. In all these cases, somatostatin binding is of high affinity and specific for bioactive somatostatin analogs. Somatostatin receptors are also expressed in pathological states, particularly in neuroendocrine tumors of the gastrointestinal tract. Ninety percent of the carcinoids and a majority of islet-cell carcinomas, including their metastases, usually have a high density of somatostatin receptors. Only 10 percent of the colorectal carcinomas and none of the exocrine pancreatic carcinomas, however, contain somatostatin receptors. The somatostatin receptors in tumors are identified with in vitro binding methods or with in vivo imaging techniques; the latter allow the precise localization of the tumors and their metastases in the patients. Since somatostatin receptors in gastroenteropancreatic tumors are functional, their identification can be used to assess the therapeutic efficacy of octreotide to inhibit excessive hormone release in the patients.     

Purinergic signalling in the gastrointestinal tract and related organs in health and disease

Purinergic signalling plays major roles in the physiology and pathophysiology of digestive organs. Adenosine 5′-triphosphate (ATP), together with nitric oxide and vasoactive intestinal peptide, is a cotransmitter in non-adrenergic, non-cholinergic inhibitory neuromuscular transmission. P2X and P2Y receptors are widely expressed in myenteric and submucous enteric plexuses and participate in sympathetic transmission and neuromodulation involved in enteric reflex activities, as well as influencing gastric and intestinal epithelial secretion and vascular activities. Involvement of purinergic signalling has been identified in a variety of diseases, including inflammatory bowel disease, ischaemia, diabetes and cancer. Purinergic mechanosensory transduction forms the basis of enteric nociception, where ATP released from mucosal epithelial cells by distension activates nociceptive subepithelial primary afferent sensory fibres expressing P2X3 receptors to send messages to the pain centres in the central nervous system via interneurons in the spinal cord. Purinergic signalling is also involved in salivary gland and bile duct secretion.     

Contractile effects of ghrelin-related peptides on the chicken gastrointestinal tract in vitro

Ghrelin is an endogenous ligand for growth hormone secretagogue receptor (GHS-R), and it stimulates growth hormone (GH) release, food intake and gastrointestinal motility in mammals. Ghrelin has also been identified in the chicken, but this peptide inhibits food intake in the chicken. We examined the effects of ghrelin and related peptides on contractility of the isolated chicken gastrointestinal tract in vitro. Among ghrelin-related peptides examined (1 microM of rat ghrelin, human ghrelin, chicken ghrelin and growth hormone releasing peptide-6 (GHRP-6)), only chicken ghrelin was effective on contraction of the chicken gastrointestinal tract. Des-acyl chicken ghrelin was ineffective, suggesting that octanoylation at Ser3 residue of chicken ghrelin was essential for inducing the contraction. Amplitude of chicken ghrelin-induced contraction was region-specific: highest in the crop and colon, moderate in the esophagus and proventriculus, and weak in the small intestine. The contractile response to chicken ghrelin in the crop was not affected by tetrodotoxin (TTX), but that in the proventriculus was decreased by TTX and atropine to the same extents. D-Lys3-GHRP-6 (a GHS-R antagonist) caused a transient contraction and inhibited the effect of chicken ghrelin without affecting the high-K+-induced contraction. Chicken ghrelin potentiated electrical field stimulation-induced cholinergic contraction without affecting the responsiveness to bath-applied carbachol in the proventriculus. The location of GHS-R differs in the crop (smooth muscle) and proventriculus (smooth muscle and enteric neurons). These results indicate that ghrelin has contractile activity on gastrointestinal tract in the chicken in vitro, and the effect was region-specific. The action would be mediated through the GHS-R, which is highly sensitive to chicken ghrelin.     

An immunohistochemical study on the distribution of endocrine cells in the chicken gastrointestinal tract

The distribution and the frequency of occurrence of nine types of gut endocrine cells were revealed using immunohistochemical methods in eight portions from the gastrointestinal tract of the chicken (Gallus gallus var domestica). In the proventriculus, somatostatin- and gastrin-releasing polypeptide (GRP)-immunoreactive cells were commonly found. Serotonin-, pancreatic glucagon-, and enteroglucagon-immunoreactive cells were uncommon. Avian pancreatic polypeptide (APP)-immunoreactive cells were rare. In the gizzard, numerous GRP-, and a small number of somatostatin-immunoreactive cells were observed. The pyloric region was characterized by the presence of abundant gastrin-, somatostatin-, and neurotensin-immunoreactive cells. Numerous serotonin-immunoreactive cells were detected in all portions of the intestine. Moderate numbers of neurotensin-immunoreactive cells were detected in all portions of the intestine except for the cecum. A few gastrin- and somatostatin-immunoreactive cells were detected in the duodenum and jejunum. A small number of pancreatic glucagon-immunoreactive cells were detected in the jejunum and ileum. Enteroglucagon-immunoreactive cells were detected in the small intestine in increasing numbers forwards the ileum. Motilin-immunoreactive cells were rare in the small intestine.     

Age-dependent reduction of ghrelin- and motilin-induced contractile activity in the chicken gastrointestinal tract

Ghrelin is an endogenous ligand for growth hormone secretagogue-receptor 1a (GHS-R1a) and stimulates gastrointestinal (GI) motility in the chicken. Since ghrelin stimulates GH release, which regulates growth, it might be interesting to compare ghrelin-induced responses in GI tract of different-aged chickens. Motilin is a ghrelin-related gut peptide that induces strong contraction in the small intestine. Aim of this study was to clarify age-dependent changes in ghrelin- and motilin-induced contractions of the chicken GI tract and expression of their receptor mRNAs. Chicken ghrelin caused contraction of the crop and proventriculus. Ghrelin-induced contraction in the proventriculus decreased gradually up to 100 days after hatching, but the responses to ghrelin in the crop were the same during the growth period. GHS-R1a mRNA expression in the crop tended to increase, but that in the proventriculus decreased depending on the age. Chicken motilin caused contraction of the chicken GI tract. Atropine decreased the responses to motilin in the proventriculus but not in the ileum. Motilin-induced contraction in the proventriculus but not that in the ileum decreased depending on post-hatching days. On the other hand, motilin receptor mRNA expression in every region of the GI tract decreased with age, but the decrease was more marked in the proventriculus than in the ileum. In conclusion, ghrelin- and motilin-induced GI contractions selectively decreased in the chicken proventriculus depending on post-hatching days, probably due to the age-related decrease in respective receptors expression. The results suggest an age-related contribution of ghrelin and motilin to the regulation of chicken GI motility.     

Plasmid profiling and curing of Lactobacillus strains isolated from the gastrointestinal tract of chicken

In this study, we assessed the susceptibility of 12 Lactobacillus strains, all of which had been isolated from the gastrointestinal tracts of chicken, to three antibiotics (chloramphenicol, erythromycin and tetracycline) used commonly as selective markers in transformation studies of lactic acid bacteria. Among these strains, 17%, 58%, and 25% were found to exhibit a high degree of resistance to 200 microg/ml of tetracycline, erythromycin, and chloramphenicol, respectively. Seven of the 12 Lactobacillus strains exhibiting resistance to at least 50 microg/ml of chloramphenicol or erythromycin, and five strains exhibiting resistance to at least 50 microg/ml of tetracycline, were subsequently subjected to plasmid curing with chemical curing agents, such as novobiocin, acriflavin, SDS, and ethidium bromide. In no cases did the antibiotic resistance of these strains prove to be curable, with the exception of the erythromycin resistance exhibited by five Lactobacillus strains (L. acidophilus I16 and I26, L. fermentum I24 and C17, and L. brevis C10). Analysis of the plasmid profiles of these five cured derivatives revealed that all of the derivatives, except for L. acidophilus I16, possessed profiles similar to those of wild-type strains. The curing of L. acidophilus I16 was accompanied by the loss of 4.4 kb, 6.1 kb, and 11.5 kb plasmids.     

Prostaglandins: effects on the gastrointestinal tract

Several prostaglandins have been shown to exert five major gastrointestinal actions. Inhibition of gastric acid secretion, orally and parenterally. Antiulcer activity (they prevent gastric and duodenal ulcers produced experimentally in animals, and they accelerate the rate of healing of duodenal ulcers in humans). Cytoprotection for the stomach, the small and the large intestine. Cytoprotection is defined as the property of many prostaglandins to protect the mucosa of the stomach and intestine from becoming inflamed and necrotic when this mucosa is exposed to noxious agents. Cytoprotection is separate from, and unrelated to, inhibition of gastric secretion. In humans, certain prostaglandins of the E type given at very low doses prevent gastric bleeding produced by aspirin and indomethacin. Stimulation of intestinal secretion, through increase of cyclic AMP formation. Stimulation of smooth muscle contraction. Certain prostaglandins are likely to be beneficial in the treatment of gastric ulcers, stress ulcers, duodenal ulcers, and perhaps gastritis and certain forms of inflammatory bowel disease.     

Transformation of, and heterologous protein expression in, Lactobacillus agilis and Lactobacillus vaginalis isolates from the chicken gastrointestinal tract

Lactobacilli are naturally found in the gastrointestinal tract of chickens, and there is interest in utilizing autochthonous strains for the delivery of therapeutic proteins. Previously we identified three chicken-derived Lactobacillus strains, Lactobacillus agilis La3, Lactobacillus vaginalis Lv5, and Lactobacillus crispatus Lc9, which persist in the gastrointestinal tract of chickens fed either a commercial or high-protein diet. In the current study, we investigated the ability to electrotransform these strains, determined plasmid vector stability, and compared reporter gene expression directed by several different promoters. The La3 and Lv5 strains were reproducibly transformed with efficiencies of 10(8) and 10(6) transformants per microgram of plasmid DNA, respectively. The third strain tested, L. crispatus Lc9, was recalcitrant to all transformation protocols examined. The plasmid vectors pTRK563 and pTRKH2 were maintained over 100 generations in La3 and Lv5, respectively. The ability of La3 and Lv5 to express the heterologous reporter gene gfp was analyzed using heterologous and homologous promoters. Transformants of both La3 and Lv5 containing the La3 ldhL promoter were the most fluorescent. To our knowledge, this is the first report of successful transformation and heterologous protein expression in L. agilis and L. vaginalis. The ability of these strains to express heterologous proteins in vitro indicates their potential utility as in vivo delivery vectors for therapeutic peptides to the chicken gastrointestinal tract.     

The distribution and ontogeny of gastrin/CCK-, somatostatin- and neurotensin-immunoreactive cells in the gastrointestinal tract of the chicken

The distribution and time of appearance of cells with gastrin/CCK-, neurotensin- and somatostatin-like immunoreactivity were studied in samples from eight regions of the gastrointestinal tract of chick embryos from 11 days of incubation to hatching. No immunoreactive cells were found in any region at 11 days of incubation. Somatostatin- and neurotensin-immunoreactive cells appeared for the first time in the proventriculus, pyloric region and duodenum at 12 days of incubation with cells immunoreactive for neurotensin occurring in the rectum at the same stage. Gastrin/CCK-immunoreactive cells were detected in the small intestine first at 14 days and in the pyloric region two days later. Cells immunoreactive for somatostatin and neurotensin appeared in the upper and lower ileum at 14 days of incubation for the first time; neurotensin-immunoreactive cells, present in the caecum at 14 and 16 days, were rare. Cells of all three types were plentiful in the pyloric region by 17 1/2 days of incubation. No immunoreactive cells were detected in the gizzard at any stage studied. Endocrine cells were present in the relatively undifferentiated surface epithelium which occurs throughout the gastrointestinal tract of chick embryos at 12 days of incubation. Thereafter cells of all three types were detected in the glandular epithelium at or very soon after morphogenesis and differentiation of the latter had occurred.     

Probiotic potential of lactic acid bacteria isolated from chicken gastrointestinal digestive tract

This study was conducted in order to evaluate the probiotic properties of lactic acid bacteria (LAB) isolated from intestinal tract of broilers and Thai indigenous chickens. The major properties, including the gastric juice and bile salts tolerance, starch, protein and lipid digesting capabilities, and the inhibition on certain pathogenic bacteria were investigated. Three-hundred and twenty-two and 226 LAB strains were isolated from ten broilers and eight Thai indigenous chickens, respectively. The gastrointestinal transit tolerance of these 548 isolates was determined by exposing washed cell suspension at 41°C to simulated gastric juice (pH 2.5) containing pepsin (3 mg ml⁻¹), and to simulated small intestinal juice (pH 8.0) in the presence of pancreatin (1 mg ml⁻¹) and 7% fresh chicken bile, mimicking the gastrointestinal environment. The survival of 20 isolates was found after passing through the gastrointestinal conditions. The survival rates of six strains; KT3L20, KT2CR5, KT10L22, KT5S19, KT4S13 and PM1L12 from the sequential study were 43.68, 37.56, 33.84, 32.89, 31.37 and 27.19%, respectively. Twelve isolates exhibited protein digestion on agar plate but no isolates showed the ability to digest starch and lipid. All 20 LAB showed the antimicrobial activity against Salmonella sp., Staphylococcus aureus and Escherichia coli except one strain which did not show the inhibitory activity toward E. coli. Accordingly, five isolates of selected LAB (KT2L24, KT3L20, KT4S13, KT3CE27 and KT8S16) can be classified as the best probiotics and were identified as Enterococcus faecalis, Enterococcus durans, Enterococcus faecium, Pediococcus pentosaceus, and Enterococcus faecium, respectively. The survival rate of microencapsulation of E. durans KT3L20 under simulated small intestine juice after sequential of simulated gastric juice was also investigated. An extrusion technique exhibited a higher survival rate than emulsion technique and free cell, respectively.     

Interactions of the flavonoid naringenin in the gastrointestinal tract and the influence of glycosylation

Previous studies have documented the direct antioxidant effects of estradiol, and it is tempting to ascribe the antiapoptosis effects of estradiol to its scavenging of reactive oxygen species. However, recent reports have also demonstrated that long-term exposure of MCF-7 human breast cancer cells to estradiol results in estrogen receptor- and estradiol dose-dependent overexpression of the antiapoptosis gene, bcl-2. We have used the pattern of protection of membrane phospholipids from oxidation as a probe to separate these direct and indirect effects of estradiol from one another. Immediate exposure to estradiol non-specifically protects all membrane phospholipids from oxidation by the diazo radical initiator, AMVN. This implies the direct antioxidant activity of estradiol in this system. In contrast, long-term exposure, with associated increased expression of bcl-2, protects only phosphatidylserine, the oxidation of which is a critical component of the final common pathway for apoptosis. This bcl-2-mediated indirect effect of estradiol is accompanied by prevention of apoptosis in MCF-7 cells.     

Breathing life into pathogens: the influence of oxygen on bacterial virulence and host responses in the gastrointestinal tract

The gastrointestinal tract provides a variety of environmental challenges to any bacterium seeking to successfully colonize or cause disease in a host. A major obstacle is the varied oxygen concentrations encountered at different sites in the intestine. Here we review the mechanisms bacterial pathogens utilize to sense oxygen within the gastrointestinal tract, and recent insights into how this acts as a signal to trigger virulence and to modulate host responses.     

Effects of gamma-irradiation on survival, growth and productivity of broiler chicken

In experiments with broiler chicken the influence of gamma-irradiation (137Cs) to survive and productivity of meat poultry was studied. LD50/30 increased from 10.0 to 18.7 Gy with increasing of the age of the irradiated chicken from 3 to 40 days and reduced from 18.3 to 11.9 Gy with increasing of a dose rate from 1.0 to 40.0 Gy/h. As a rule, death of chicken was observed between 4th and 15th days after the exposure; the most early dates of poultry death were found at irradiation dose rate of 40.0 Gy/h. The exposure to doses of 8-20 Gy resulted in stunted growth; in comparison with control group the mass reduced by 22-32 g per each 1 Gy, lowering of meat productivity by 36%.     

Microbiota and autoimmune disease: the hosted self

The trillions of microbial symbionts normally hosted by mammals have important influences on the development and function of the immune system. We highlight recently discovered cellular and molecular mechanisms by which they impact autoimmune diseases--in particular, gut-distal disorders. Besides provoking a reconsideration of the definition of immunological "self" and "nonself," these new findings evoke exciting possibilities for the discovery of a whole new class of immunomodulatory molecules.     

Metagenomic bacterial community profiles of chicken embryo gastrointestinal tract by using T-RFLP analysis

Thirty microbial phylotypes of microorganisms were found in the gastrointestinal tract of chicken belonging to the Hajseks White breed, and 38 phylotypes were found in the gastrointestinal tract of chicken belonging to the Hajseks Brown breed. The microbiome of the gastrointestinal tract of the chicken embryos of the Hajseks White breed was dominated by the typical representatives of avian intestinal microflora—bacteria of the family Enterobacteriaceae (47.3%), orders Actinomycetales (13.6%) and Bifidobacteriales (20.6%), and the family Lachnospiraceae (1.1%). The microbiome of the gastrointestinal tract of the chicken embryos of the Hajseks Brown breed was dominated by the pathogenic bacteria of the order Rickettsiales (94.8%). The metagenome of gastrointestinal tract of both breeds also contained a small number of genes of unidentified bacteria.     

Antithetical effects of corticosterone and dibutyryl cAMP on adenosine deaminase in the gastrointestinal tract of chicken during postnatal development

Liver fatty acid binding protein (L-FABP) is highly expressed in both enterocytes and hepatocytes and binds multiple ligands, including saturated (SFA), unsaturated fatty acids (PUFA), and cholesterol. L-fabp ^?/? mice were protected against obesity and hepatic steatosis on a high saturated fat (SF), high cholesterol “Western” diet and manifested a similar phenotype when fed with a high SF, low cholesterol diet. There were no significant differences in fecal fat content or food consumption between the genotypes, and fatty acid (FA) oxidation was reduced, rather than increased, in SF-fed L-fabp ^?/? mice as evidenced by decreased heat production and serum ketones. In contrast to mice fed with a SF diet, L-fabp ^?/? mice fed with a high PUFA diet were not protected against obesity and hepatic steatosis. These observations together suggest that L-fabp ^?/? mice exhibit a specific defect in the metabolism of SFA, possibly reflecting altered kinetics of FA utilization. In support of this possibility, microarray analysis of muscle from Western diet-fed mice revealed alterations in genes regulating glucose uptake and FA synthesis. In addition, intestinal cholesterol absorption was decreased in L-fabp ^?/? mice. On the other hand, and in striking contrast to other reports, female L-fabp ^?/? mice fed with low fat, high cholesterol diets gained slightly less weight than control mice, with minor reductions in hepatic triglyceride content. Together these data indicate a role for L-FABP in intestinal trafficking of both SFA and cholesterol.