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R de Giorgio

Publications and source records attributed to R de Giorgio.

9 recordsLinked to original sources
PubMed2006

Constitutive expression of cyclooxygenase-2 in the neuromuscular compartment of normal human colon.

Prostaglandins regulate various functions throughout the gastrointestinal system. Their biosynthesis depends on cyclooxygenase isoforms, named COX-1 and COX-2. The initial hypothesis that COX-2 is an inducible enzyme has been challenged and its constitutive expression in the stomach has been established. In this study, an immunohistochemical analysis was performed to evaluate the distribution and cellular localization of COX-2 in normal human colon. Colonic surgical specimens were processed for COX-2, protein HuC/HuD, neurofilament, S-100 protein and CD117/c-kit immunodetection. COX-2 protein was found to be constitutively expressed in the colonic wall: detectable amounts were localized in mucosal, submucosal and muscular layers, mainly in the neuromuscular compartment. In particular, COX-2 was expressed in muscularis mucosae, submucosal ganglia, longitudinal muscle layer and myenteric ganglia, the neurons of which displayed different degrees of immunostaining. Intramuscular interstitial cells of Cajal, regarded as important sites for the regulation of enteric neuromuscular activity, were also partly COX-2 immunoreactive. This study provides a detailed mapping of COX-2 expression in human colon, and allows better understanding of the roles played by this isoenzyme in gut physiology.

Blotting, Western↗
PubMed2001

Review article: Helicobacter pylori, mucosal inflammation and symptom perception--new insights into an old hypothesis.

The role of Helicobacter pylori and the accompanying mucosal inflammatory response in functional dyspepsia is still undefined. Human and animal studies have clearly demonstrated a link between intestinal mucosal inflammation and changes in sensory-motor function. Growing clinical and basic evidence supports the concept that a similar paradigm may occur in H. pylori-related dyspepsia. The infection may both induce gastric dysmotility and trigger neuroplastic changes in the afferent neural pathways leading to visceral hyperalgesia. A reduction of central antinociceptive control systems may also play a pathophysiological role. H. pylori eradication has provided disappointing results in terms of improvement of symptoms. This may reflect the long-term recovery of neuroplastic changes occurring in the afferent nervous system or, alternatively, the incomplete resolution of gastritis and the persistent production of inflammatory mediators by resident cells in the muscularis externa. The identification of these mechanisms may provide a better understanding of the pathophysiology of H. pylori-related dyspepsia and prompt innovative therapeutic approaches.

Animals↗
PubMed1998

Plasma cholecystokinin and neurotensin after an ordinary meal in humans. A prolonged time study.

BACKGROUND/AIM: Ingestion of a meal causes the release of cholecystokinin and neurotensin into the circulation, but little is known about the duration of this release. METHODS: Six healthy volunteers were studied. Blood samples for cholecystokinin, neurotensin and gastrin assessment were drawn before and after consumption of a typical Italian lunch. Postprandial samples were obtained every hour for a total of 10 hours. All peptides were measured using previously validated radioimmunoassays. RESULTS: Ingestion of the meal caused a prompt and significant increase in plasma levels of all three peptides. Cholecystokinin remained elevated for about 7 hours and then tended to return towards basal values, whereas the increase of neurotensin persisted for the entire period of the study (10 hours). Gastrin remained elevated for about 5 hours and then declined. The integrated CCK and gastrin responses during the initial postprandial hours were greater than those in the late hours, whereas the integrated neurotensin response during the initial hours was lower than that in the late hours. CONCLUSIONS: The results indicate that, after an ordinary meal, cholecystokinin is released into the circulation for about 7 hours, much longer than previously reported (3-4 hours). The release of neurotensin begins soon after the meal and persists even longer, for at least 10 hours. Possible physiological implications of these findings are discussed.

Adult↗
PubMed1997

Somatostatin 2A receptor is expressed by enteric neurons, and by interstitial cells of Cajal and enterochromaffin-like cells of the gastrointestinal tract.

Somatostatin exerts multiple effects by activating distinct G protein-coupled receptors. Here we report the cellular sites of expression of the somatostatin subtype 2A (sst2A) receptor in the rat enteric nervous system by using a C-terminus-specific, affinity-purified antiserum and immunohistochemistry. Antibody specificity was confirmed by the cell surface staining of human embryonic kidney 293 cells expressing the sst2A receptor, the lack of staining of cells expressing the somatostatin subtype 2B receptor, and the abolition of staining by preincubating the antiserum with the C-terminus peptide used for immunization, SSt2A(361-369). The SSt2A receptor antibody recognized a broad 80 kDa band on Western blots of membranes prepared from cells transfected with sst2A receptor cDNA; following receptor membrane deglycosylation, the antibody detected an additional 40 kDa band. In the enteric nervous system, the sst2A antibody primarily stained neurons of the myenteric and submucosal plexuses, and abundant fibers distributed to the muscle, mucosa, and vasculature. Immunoreactive staining was also observed in non-neuronal cells, including presumed interstitial cells of Cajal of the intestine and enterochromaffin-like cells of the stomach. Fibers expressing sst2A receptor immunoreactivity were often in close proximity to D cells of the gastric and intestinal mucosa. Colocalization of somatostatin and sst2A receptor immunoreactivities was not observed in endocrine cells nor in enteric neurons. Double-label immunohistochemistry revealed colocalization of sst2A and vasoactive intestinal peptide immunoreactivities in enteric neurons. The multiple types of cells expressing the sst2A receptor, including enteric neurons and non-neuronal structures, in addition to the relationship between somatostatin and sst2A receptor elements, provide evidence that the sst2A receptor mediates somatostatin effects in the gastrointestinal tract via neuronal and paracrine pathways.

Amino Acid Sequence↗
PubMed1996

Cellular localization of Pan-trk immunoreactivity and trkC mRNA in the enteric nervous system.

The members of the trk family of tyrosine receptor kinases, trkA, trkB, and trkC, are the functional receptors for neurotrophins, a family of related neurotrophic factors. In this study, we investigated 1) the distribution of neurotrophin receptors in the developing and adult rat digestive tract with a pan-trk antibody that recognizes all known trks and 2) the cellular localization of trk-encoding mRNAs in the adult gut with single-stranded RNA probes specific for trkA, trkB, and trkC. In the developing myenteric plexus, trk immunoreactivity was present at embryonic day (ED) 14. Cells and fibers immunoreactive for trk could be visualized in the myenteric plexus at ED 16. At this age, dense staining was found in thick bundles of fibers in proximity to the myenteric plexus in the longitudinal muscle and in association with blood vessels in the mesentery. At ED 18, trk immunoreactivity was also seen in thin processes running from the myenteric plexus into the circular muscle, and in fibers and cells in intrapancreatic ganglia. By ED 20, immunoreactive staining was quite dense in both the myenteric and submucosal plexuses. At birth, virtually all enteric ganglia displayed strong trk immunoreactivity; the intensity of the staining at this age made it difficult to discern individual cells. During postnatal development, there was a decrease in cell body staining and an increase in the density of trk-containing fibers that became widely distributed to the gut wall and pancreas. The adult pattern of trk immunoreactivity was established between postnatal days 5 and 10. In adults, trk immunoreactivity was found in numerous enteric and intrapancreatic ganglion cells and in dense networks of fibers innervating all the layers of the gut, the pancreas, and vasculature. The trkC mRNA was expressed in adult enteric ganglion cells of both the myenteric and submucous plexus. By contrast, the trkA and trkB mRNAs could not be detected in enteric ganglia. All three trk mRNAs were expressed in dorsal root ganglia, which were used as positive controls. The density and wide distribution of trk immunoreactivity together with its persistence in adulthood support the concept that neurotrophins play a broad role in the digestive system from development through adult life, perhaps being involved in differentiation, phenotypic expression, and tissue maintenance. The presence of trkC mRNA in enteric neurons along with recent evidence that neurotrophin-3 plays a role in the development of the enteric nervous system suggest that trkC and neurotrophin-3 are a major neurotrophin system in the gastrointestinal tract.

Animals↗
PubMed1995

Differential expression of two vesicular monoamine transporters.

Specific transport proteins package classical neurotransmitters into vesicles so that their release can be regulated by neural activity. Previous studies have suggested that a single activity mediates the vesicular transport of monoamines in the adrenal gland, brain, and other tissues such as mast cells and platelets. However, molecular cloning has recently identified two vesicular transporters for monoamines. Although the predicted proteins are closely related in sequence, they show a range of differences in their physiologic and pharmacologic properties. To clarify further the biological significance of the observed functional differences, we have generated anti-peptide antibodies to the C-termini of the two transporters and used them to determine the distribution and localization of the proteins in the rat. We have detected expression of vesicular monoamine transporter 1 (VMAT1) in adrenal chromaffin cells but not in neural cells. Interestingly, some adrenal chromaffin cells also express VMAT2 but the amount of VMAT2 relative to VMAT1 appears much lower than in the bovine adrenal gland. In contrast, sympathetic ganglion cells express only VMAT2, as do enteric neurons and enterochromaffin-like cells of the stomach. Thus, although adrenal chromaffin cells, sympathetic and enteric neurons derive from the neural crest, they express different vesicular amine transporters. In the CNS, dopamine, norepinephrine, epinephrine, 5-HT, and histamine cell groups all express VMAT2. These findings are consistent with the functional characteristics of VMAT1 and VMAT2 and help to explain several classic pharmacological observations. VMAT2-immunoreactivity is generally stronger in cell bodies, proximal dendrites and axonal processes, indicating the potential for monoamine storage at each of these sites. Surprisingly, dopaminergic interneurons in the olfactory bulb show no detectable immunoreactivity for either VMAT1 or VMAT2.

Adrenal Glands↗