Distribution of prostaglandin-sensitive adenylate cyclase in human upper gastrointestinal tract

The localization of the prostaglandin-sensitive adenylate cyclase in the upper gastrointestinal tract in human beings was studied. The prostaglandin-sensitive enzyme was almost evenly distributed throughout the fundic, antral and duodenal mucosa. The enhancement of enzyme activity in the presence of maximally effective prostaglandin concentrations exceeded basal levels by about 200%. The physiological role of the prostaglandin sensitive adenylate cyclase in gastric and duodenal function, however, remains to be established.     

Distribution and characterization of endogenous benzodiazepine receptor ligand (endozepine)-like peptides in the rat gastrointestinal tract

Endozepine is the generic name for a family of peptides that are capable of displacing benzodiazepines and the 3-carboxylate ester of beta-carboline from their specific binding sites on synaptosomal membranes. The 104-amino acid polypeptide diazepam-binding inhibitor (DBI) and the octadecaneuropeptide (ODN) generated by tryptic digestion of DBI are two members of the endozepine family. In the present study we have used RIA, HPLC, in situ hybridization, and immunohistochemical techniques to identify and localize endozepine-like molecules in the rat gastrointestinal tract. Significant amounts of endozepine-like immunoreactivity (LI) were detected throughout the gut; the highest concentrations were found in the duodenum and antrum. HPLC analysis revealed that the immunoreactive material eluted as a major peak with a higher retention time than that of synthetic ODN. The distribution of the immunoreactive peptide(s) was studied using the peroxidase-antiperoxidase technique at the light microscope level. Endozepine-LI was localized only in the epithelial cell layer of the intestine in both goblet cells and enterocytes. In the stomach, endozepine-LI appeared to be restricted to deep layer of the epithelial cells. The diffuse neuroendocrine cells (amine precursor uptake and decarboxylation system) as well as myenteric and neuronal cells were devoid of immunoreactivity. A good correlation was observed between RIA and immunocytochemical data, in that the esophagus, which contained very low concentrations of endozepine-LI, also exhibited weak immunostaining of secretory cells. In situ hybridization using a 35S-labeled cRNA probe showed that endozepine mRNA was located in the mucosa. Taken together, these results show that in the rat, epithelial cells synthesize endozepine-LI material. Since epithelial cells also contain a high density of peripheral-type benzodiazepine-binding sites, our data indicate that endozepines may play a role in water, electrolyte, and/or mucus regulation in the rat gastrointestinal tract. The occurrence of high levels of endozepine-LI in the rat stomach also suggests that endozepines can be involved in the regulation of gastric acid secretion through modulation of local gamma-aminobutyric acid-ergic neurotransmission.     

Glucagon-related peptides in the human gastrointestinal mucosa

Summary We studied the chromatographic profile and the distribution of glucagon-related peptides in the human gastrointestinal mucosa, using radioimmunoassays directed against the glucagon 6–15 and 19–29 sequences, and against the glicentin sequences 15–30 and 61–69, and a radioreceptor assay for glucagon. Very small amounts of glucagon-related peptides were found in the gastric mucosa, whereas at least four different components could be identified in the distal intestine. One component (mean concentration 130 pmol/g ileal mucosa) is similar to porcine glicentin for size and C-terminal extension, but differs from the glucagon part of the molecule in the N-terminal extension. A second component (mean concentration 131 pmol/g) is probably identical to porcine peak II enteroglucagon (glicentin 33–69), and a third component (7.9 pmol/g) seems to be identical with glucagon. A fourth component containing the glucagon sequence plus an N-terminal extension was also identified (1.7 pmol/g). Thus the human intestinal mucosa contains large amounts of peptides containing the glucagon sequence; at least one of these probably also possesses glucagon-like bioactivity. The proposed structures of the four components are consistent with the base sequence of the first half of the human glucagon gene.     

Spirochete-like organisms in the human gastrointestinal tract

Spirochete-like organisms were first detected in human feces in 1884. In the century since that observation an appreciable amount of epidemiologic and morphologic information has been published; nevertheless, it is not known how many species of cultivable human intestinal spirochetes exist, nor is the role of these organisms in health and disease known. Recent advances in microbiologic techniques, coupled with the recognition that the rate of carriage of such spirochetes in certain populations is approximately 30%-40%, should provide the impetus for careful scientific study of these organisms and of their importance-if any-to human health.     

Neuroendocrine peptides of the gastrointestinal tract of an animal model of human type 2 diabetes mellitus

We studied ten obese diabetic mice (Umeå/ Bom-ob) and 10 homozygous lean controls aged 21 weeks. The concentration of several neuroendocrine peptides was determined by radioimmunoassay of tissue extracts of antrum, duodenum and distal colon. The neuroendocrine peptides that we investigated were: secretin, gastric inhibitory polypeptide (GIP), gastrin, motilin, peptide YY (PYY), somatostatin, vasoactive intestinal polypeptide (VIP), substance P, neurotensin, neuropeptide Y (NPY) and galanin. In the antrum, gastrin, somatostatin, VIP, substance P and NPY concentrations were significantly lower in obese diabetic mice than in the lean controls. There was no statistical difference between the obese mice and lean controls for neurotensin and galanin content. In the duodenum, the concentration of substance P was lower in the obese diabetic mice than in lean mice. There was no statistical difference between obese diabetic mice and lean controls regarding the concentration of secretin, GIP, motilin, gastrin, somatostatin, VIP, neurotensin, NPY or galanin. In the colon, the levels of PYY, somatostatin, VIP, substance P, NPY and galanin were significantly lower in the obese diabetic mice than the lean controls. The concentration of neurotensin in the obese mice did not differ from that in the lean controls. The present study showed that the neuroendocrine system is disturbed in an animal model of human type 2 diabetes and that this disturbance differs from that observed in other animal models of human type 1 diabetes. The present findings may have some implications for the gastrointestinal dysfunction observed in patients with type 2 diabetes.     

Histochemistry of microvascular smooth muscle in the gastrointestinal tract.

Representative enzymes and substrates of the major metabolic pathways were analyzed and compared in submucosal arteriolar smooth muscle of the stomach, ileum, and colon by histochemical methods. Anaerobic glycolysis was represented by lactate dehydrogenase, the Krebs cycle by isocitrate dehydrogenase, and the respiratory chain by cytochrome oxidase. The hexose monophosphate shunt was represented by glucose-6-phosphate dehydrogenase, while fat utilization was demonstrated by β-hydroxybutyrate. Glycogen, cholesterol, free fatty acid, and neutral fat levels were also determined. The results of the study indicate that, in general, the ileal microvessels are metabolically more diverse than those of the stomach and colon. Unlike stomach and colon microvessels, arteriolar smooth muscle in the ileum maintains large endogenous stores of carbohydrates and fats. In addition, ileal microvessels possess a high potential for energy production via each of the major metabolic pathways. The metabolic profile of colonic microvessels was similar to that of ileum except for the absence of endogenous substrate stores. Stomach microvessels also lacked endogenous substrate stores; yet, unlike ileum and colon microvessels, no discernible glucose-6-phosphate dehydrogenase activity was determined for these vessels. The results of this study indicate that the metabolic machinery of vascular smooth muscle varies markedly between the functionally related organs of the gastrointestinal tract.     

Occurrence and polymorphism of bombesin-like peptides in the gastrointestinal tract of birds and mammals

The gastrointestinal tract of mammals and birds, especially stomach and upper small intestine, contains bombesin-like peptides. This has been unequivocally demonstrated by radioimmunoassay and bioassay. Concentrations of bombesin-like activity may range from a few ng to 500-600 ng per g fresh tissue. Last values refer to the chicken proventriculus, which has been the object of a more thorough investigation. The bombesin-like peptide of the chicken proventriculus showed a marked heterogeneity. All forms probably stem from a pro-bombesin, a large precursor molecule which is insoluble in methanol, acetone, and even boiling water, but may be cleaved by acid hydrolysis. Methanol extracts contain at least two forms of the bombesin-like peptide; HCl extracts at least three forms; HCl extracts of the residue of methanol extraction at least four forms. Whereas some forms--for example, the methanol extractable forms--probably pre-exist in the tissue, other forms may be artefacts arising from acid treatment. The various forms may be distinguished from each other not only by their elution profile, but also by bioassay. In fact, though all forms show the activity spectrum characteristic for the amphibian bombesin-like peptides, they present considerable quantitative differences in activity. Pro-bombesin(s) probably occur also in the rat and guinea-pig stomach; similarly, a clear-cut heterogeneity is appreciable for the bombesin-like peptide of the human gastric mucosa.     

Sensory testing of the human gastrointestinal tract

The objective of this appraisal is to shed light on the various approaches to screen sensory information in the human gut. Understanding and characterization of sensory symptoms in gastrointestinal disorders is poor. Experimental methods allowing the investigator to control stimulus intensity and modality, as well as using validated methods for assessing sensory response have contributed to the understanding of pain mechanisms. Mechanical stimulation based on impedance planimetry allows direct recordings of luminal cross-sectional areas, and combined with ultrasound and magnetic resonance imaging, the contribution of different gut layers can be estimated. Electrical stimulation depolarizes free nerve endings non-selectively. Consequently, the stimulation paradigm （single, train, tetanic） influences the involved sensory nerves. Visual controlled electrical stimulation combines the probes with an endoscopic approach, which allows the investigator to inspect and obtain small biopsies from the stimulation site. Thermal stimulation （cold or warm） activates selectively mucosal receptors, and chemical substances such as acid and capsaicin （either alone or in combination） are used to evoke pain and sensitization. The possibility of multimodal （e.g. mechanical, electrical, thermal and chemical） stimulation in different gut segments has developed visceral pain research. The major advantage is involvement of distinctive receptors, various sensory nerves and different pain pathways mimicking clinical pain that favors investigation of central pain mechanisms involved in allodynia, hyperalgesia and referred pain. As impairment of descending control mechanisms partly underlies the pathogenesis in chronic pain, a cold pressor test that indirectly stimulates such control mechanisms can be added. Hence, the methods undoubtedly represent a major step forward in the future characterization and treatment of patients with various diseases of the gut, which provides knowledge to dinicians about the underlying symptoms and treatment of these patients.     

Gastrin receptors in the human gastrointestinal tract and pancreas

The specific binding of 125I-labeled gastrin-17 was studied in samples of human gastric mucosa, duodenal mucosa, colonic mucosa or pancreatic tissue obtained surgically. With regard to gastric fundic mucosa, the criteria for receptor binding were studied, and saturability, high affinity, tissue specificity and hormone specificity were demonstrated. The dissociation constant for gastric fundic mucosa was 1.6 X 10(-9)M, and the binding capacity was 15 fmol/mg protein. Tissue specificity studies revealed a high degree of gastrin receptor binding in human gastric fundic mucosa, duodenal mucosa and pancreas, whereas antral mucosa and colonic mucosa demonstrated a low degree of binding.     

Hydrogen cross-feeders of the human gastrointestinal tract

Hydrogen plays a key role in many microbial metabolic pathways in the human gastrointestinal tract (GIT) that have an impact on human nutrition, health and wellbeing. Hydrogen is produced by many members of the GIT microbiota, and may be subsequently utilized by cross-feeding microbes for growth and in the production of larger molecules. Hydrogenotrophic microbes fall into three functional groups: sulfate-reducing bacteria, methanogenic archaea and acetogenic bacteria, which can convert hydrogen into hydrogen sulfide, methane and acetate, respectively. Despite different energy yields per molecule of hydrogen used between the functional groups, all three can coexist in the human GIT. The factors affecting the numerical balance of hydrogenotrophs in the GIT remain unconfirmed. There is increasing evidence linking both hydrogen sulfide and methane to GIT diseases such as irritable bowel syndrome, and strategies for the mitigation of such health problems through targeting of hydrogenotrophs constitute an important field for further investigation.     

Cytomegalovirus infection of the human gastrointestinal tract

BACKGROUND: Current interest in cytomegalovirus (CMV) is largely due to an increase in the number of cases of acquired immunodeficiency syndrome and organ transplantation in recent years. The proper recognition of CMV-infected cells in gastrointestinal mucosal biopsies is critical for effective treatment of this condition. METHODS: A total of 6580 endoscopic mucosal biopsies from 6323 patients in the 8-year period (1989-1996) were examined for CMV inclusion bodies. The endoscopic appearance and particularly the presence of ulcers were also analysed. RESULTS AND CONCLUSIONS: The prevalence of cytomegalovirus (CMV) inclusions was 9 per thousand in the gastrointestinal mucosal biopsies from an unselected group of patients. Of the 54 patients with CMV infection, 37 were immunocompromised and 17 apparently immunocompetent. Typical Cowdry inclusions and atypical inclusions were present, the latter more frequently in immunocompromised patients. The maximum prevalence of inclusions was in the oesophageal mucosa in immunocompromised individuals.     

Gastrin receptors in the human gastrointestinal tract and pancreas

The specific binding of¹²⁵I-labeled gastrin-17 was studied in samples of human gastric mucosa, duodenal mucosa, colonic mucosa or pancreatic tissue obtained surgically. With regard to gastric fundic mucosa, the criteria for receptor binding were studied, and saturability, high affinity, tissue specificity and hormone specificity were demonstrated. The dissociation constant for gastric fundic mucosa was 1.6 x 10^-9M, and the binding capacity was 15 fmol/mg protein. Tissue specificity studies revealed a high degree of gastrin receptor binding in human gastric fundic mucosa, duodenal mucosa and pancreas, whereas antral mucosa and colonic mucosa demonstrated a low degree of binding.     

Effectiveness of prokinetic agents against diseases external to the gastrointestinal tract

Prokinetic agents are effective not only for disease of the gastrointestinal (GI) tract but also for those external to the GI tract such as the central nervous system, and the respiratory, urologic, and metabolic organs. This article reviews the effectiveness of prokinetic agents against diseases external to the GI tract. Studies were identified by computerized and manual searches of the available literature. A Medline search was performed (1975–July, 2008) using the following medical subject headings: prokinetic agent, metoclopramide, domperidone, trimebutine, cisapride, itopride, mosapride, tegaserod, and human. The identified diseases for which prokinetic agents may be effective are various: bronchial asthma, chronic cough, hiccup, spontaneous bacterial peritonitis, cholelithiasis, diabetes mellitus, acute migraine, Parkinson's disease, anorexia nervosa, Tourette's disorder, urologic sequelae of spinal cord injury and of radical hysterectomy for cervical cancer, laryngeal dysfunction and so on. These agents are also useful for prevention of aspiration pneumonia during anesthesia, and in tube‐fed patients. Prokinetic agents should be a valuable addition to our currently limited pharmacological armamentarium not only for functional bowel disease, but also for diseases external to the GI tract.     

Distribution of somatostatin receptor messenger RNAs in the rat gastrointestinal tract

BACKGROUND & AIMS: The gastrointestinal (GI) tract is a major source and target of somatostatin (SRIF). Recently, five pharmacologically different SRIF receptors (sst1-5) were cloned. The cellular and tissue distribution of the sst1-5 messenger RNAs (mRNAs) were studied in the rat GI tract using in situ hybridization histochemistry (ISHH). METHODS: Two sets of (35)S-uridine triphosphate (UTP)-labeled antisense and sense riboprobes were prepared for each sst. ISHH was conducted on frozen tissue samples from rat stomach, duodenum, jejunum, ileum, colon, and pancreas. RESULTS: mRNAs of all five sst-s are widely expressed in the rat GI tract. The distribution pattern for each sst mRNA was identical with both antisense probes. No specific signal was found with any of the sense probes. Each layer of the different parts of the gut expressed mRNAs of multiple sst subtypes. All organs expressed sst3 mRNA very intensely. The lowest levels of mRNA expression for all five subtypes within the GI tract were found in the pancreas. CONCLUSIONS: The widespread expression of sst mRNAs suggests a significant role for SRIF in the regulation of GI function. (Gastroenterology 1997 Jun;112(6):1948-60)