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Biomedical subjects

D Renzi

Publications and source records attributed to D Renzi.

At least 19 recordsLinked to original sources
PubMed1998

Enhanced secretion of substance P by cytokine-stimulated rat brain endothelium cultures.

Substance P (SP) was analyzed in rat brain endothelium cultures after cytokine stimulation. SP secretion was found after stimulation with high doses of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha). High doses of interferon-gamma (INF-gamma) had no effect on this secretion. Elevated SP release was found to be associated with mRNA expression of beta-preprotachykinin (beta-PPT), precursor of SP, in the cells. Under cytokine stimulation, part of SP was bound to brain endothelial cell surface, suggesting the existence of an autocrine network for this neuropeptide. These findings suggest that SP may have an immunomodulatory action at the blood-brain barrier during inflammatory and autoimmune processes in the central nervous system.

Animals↗
PubMed1998

Substance P and vasoactive intestinal polypeptide but not calcitonin gene-related peptide concentrations are reduced in patients with moderate and severe ulcerative colitis.

BACKGROUND AND AIMS: Ulcerative colitis is a chronic inflammatory condition characterized by an altered intestinal immunoinflammatory response. Since increasing evidence indicates that neuropeptides play a key role in the regulation of gastrointestinal immune function, the aims of this study were: a) to determine tissue and plasma levels of Vasoactive Intestinal Polypeptide, Substance P, and Calcitonin Gene-Related Peptide in patients with ulcerative colitis, and b) to ascertain whether a relationship exists between tissue concentrations of neuropeptides and the histological grading of mucosal inflammation. METHODS: A total of 29 patients with active and 39 with inactive ulcerative colitis, and 16 control subjects took part in the study. Biopsy specimens of colonic mucosa and blood samples were obtained from each subject, and neuropeptide concentrations were measured by sensitive and specific radioimmunoassays. RESULTS: Both Vasoactive Intestinal Polypeptide and Substance P concentrations were found to be significantly reduced in endoscopic biopsy specimens of patients with ulcerative colitis compared to controls (p < 0.01 and p = 0.05, respectively), and the reduction appeared to be related to the degree of mucosal inflammation; in contrast, Calcitonin Gene-Related Peptide tissue levels were unchanged. In addition, there was no significant difference in the neuropeptide plasma levels between ulcerative colitis patients and control subjects. CONCLUSIONS: Taken together, our results suggest that the reduction of Vasoactive Intestinal Polypeptide and Substance P is probably a secondary phenomenon, correlated with the degree of mucosal inflammation; whatever the mechanism, the decreased availability of these neuropeptides in the local microenvironment may play an important role in the pathogenesis of ulcerative colitis, by affecting many components of the normal immune response. Moreover, based on our data, the measurement of neuropeptide plasma concentrations does not appear to be a useful tool to monitor disease activity.

Adult↗
PubMed1997

A protective role for calcitonin gene-related peptide in water-immersion stress-induced gastric ulcers in rats.

This study investigated the role of endogenous and exogenous calcitonin gene-related peptide (CGRP) in water immersion stress (WIS)-induced gastric ulcers in rats. WIS produced gastric ulcers which were inversely correlated to the decrease in CGRP-like immunoreactivity observed in the whole thickness of the corpus stomach but not in its mucosal layers. Systemic administration of CGRP (100 micrograms kg-1 s.c.) produced a significant decrease in lesion index of WIS-ulcers and this protection was inhibited by functional ablation of afferent neurons induced by capsaicin pretreatment (100 mg kg-1 s.c. in two days, a week before the experiments). These findings suggest that sensory endogenous CGRP plays a defensive role in WIS-ulcers.

Animals↗
PubMed1997

Expression of epidermal growth factor, transforming growth factor-alpha and their receptor in the human oesophagus.

Increasing evidence indicates that epidermal growth factor and transforming growth factor-alpha are involved in the maintenance of oesophageal mucosal integrity. However, their cellular origin and the exact localization of their receptor in the oesophagus are still unclear. Therefore, we examined the expression of the two growth factors and their shared receptor in the normal human oesophagus at both mRNA and protein level, by immunohistochemistry, in situ hybridization and reverse transcription-polymerase chain reaction. In addition to being expressed in the proliferative compartment of the oesophageal epithelium, the receptor was found in a variety of cells, including smooth muscle cells, submucosal gland cells and the epithelium lining their ducts. Immunohistochemically, the pattern of distribution of epidermal growth factor paralleled that of its receptor. In situ hybridization demonstrated epidermal growth factor mRNA expression in the oesophageal epithelium and submucosal glands. Additionally, amplified transcripts of predicted size were detected by reverse transcription-polymerase chain reaction, thus confirming that authentic transcripts of the growth factor exist in the normal human oesophagus. Transforming growth factor-alpha mRNA and protein expression, while similar to that of epidermal growth factor, predominated in the more differentiated cell layers of the stratified squamous epithelium. These results demonstrate that the normal oesophagus can synthesize both growth factors. Moreover, the peculiar distribution of these peptides and the concomitant expression of their receptor in multiple cell types suggest that the two growth factors may exert diverse physiological functions in the oesophagus and participate in defence and reparative events following mucosal injury.

Adult↗
PubMed1994

Capsaicin-like effect of resiniferatoxin in the rat stomach.

Neurochemical and functional studies were performed to investigate and to compare the effects of resiniferatoxin and capsaicin in the rat stomach. Neonatal administration of resiniferatoxin (0.6-1.6 mumol/kg subcutaneously (s.c.)) produced a marked decrease in gastric calcitonin gene-related peptide-like immunoreactivity in both secretory and non-secretory region of the stomach. Almost complete depletion of the peptide was determined by neonatal administration of capsaicin (164 mumol/kg s.c.). Vasoactive intestinal polypeptide-like immunoreactivity was concomitantly unaffected by resiniferatoxin or capsaicin, thus showing the selectivity of action of the neurotoxins on gastric afferent fibers. Oral administration of an equimolar dose (0.3 nmol/kg) of resiniferatoxin or capsaicin together with 50% ethanol reduced at a similar extent gastric haemorrhagic lesions produced by the mucosal barrier-breaker agent. These findings provide evidence that resiniferatoxin and capsaicin may act on a common neuronal target in the rat stomach and that the acute exciting (protective) effect is of the same magnitude.

Administration, Oral↗
PubMed1994

Influence of capsaicin-sensitive afferent fibers on acetic acid-induced chronic gastric ulcers in rats.

Accumulating evidence indicates that capsaicin-sensitive afferent fibers play a pivotal role in acute gastroprotection. However, whether they also influence healing of chronic gastric ulcers is still unknown. The effects of ablation of sensory neurons on acetic acid-induced chronic gastric ulcers in rats were investigated at morphologic and biochemical levels by computerized imaging analysis of the ulcerated area, histologic examination, and neuropeptide determination. Afferent nerve ablation, as a result of treating rats with a neurotoxic dose of capsaicin (50 + 50 mg/kg subcutaneously over 2 days), produced a significant increase in the ulcer area at 1 and 2 weeks after acetic acid injection. The delay in ulcer healing was associated with a marked and persistent decrease in tissue calcitonin gene-related peptide-like immunoreactivity, whereas gastric vasoactive intestinal polypeptide was unaffected by capsaicin pretreatment. Histologically, as compared with control rats, capsaicin-desensitized animals only differed in a slight increase in the inflammatory infiltrate during the early phase of ulcer formation. These findings suggest that capsaicin-sensitive afferent fibers may play a role in the healing of chronic experimental gastric ulcers in rats, but the underlying mechanisms remain to be elucidated and deserve further investigation.

Acetates↗
PubMed1993

Colonic vasoactive intestinal polypeptide in ulcerative colitis.

Vasoactive intestinal polypeptide (VIP) is a 28 amino acid peptide which is localised in both the central and peripheral nervous system. In the human colon VIP is found in all layers and the highest concentrations have been found in the myenteric plexus. It is known that VIP has various effects on intestinal functions: i) it is a potent stimulant of mucosal water and electrolyte secretion; ii) it is involved in the peristaltic reflex; and iii) plays an inhibitory role on immune cell function. Based on these biological effects it has been hypothesized that the intestinal mucosal immune system and inflammation may be influenced by alterations in the tissue concentrations of VIP. Some authors have demonstrated no changes in the VIP colonic content of patients with ulcerative colitis, whereas others have demonstrated a reduction. Our results, using specific radioimmunoassay, showed that there is a significant decrease of VIP in both rectal and colonic mucosa of patients with ulcerative colitis as compared to controls. The VIP decrease is selective since substance P and calcitonin gene-related peptide were unchanged in the mucosal tissue of ulcerative colitis patients and furthermore the VIP alteration is correlated to the degree of mucosal inflammation. These findings suggest that the reduction of VIP mucosal content, even if it represents a non-specific event, could influence local inflammatory response and the activity of the disease.

Colitis, Ulcerative↗
PubMed1993

Gastric lesions induced by concentrated ethanol are associated with a decrease in gastric calcitonin gene-related peptide-like immunoreactivity in rats.

Gastric calcitonin gene-related peptide-like immunoreactivity (CGRP-li) was decreased in the gastric corpus of rats treated with 75% or 96% ethanol but not with 50% ethanol. The extent of gastric lesions was related to the increasing concentrations of ethanol (50-96%). CGRP-li decrease was evident already at 5 min after the 96% ethanol challenge, whereas a peptide recovery resulted 10 days after, concomitant with the healing of gastric lesions. Ethanol (96%) produced a significant decrease of CGRP-li in the whole thickness of the gastric corpus but not in the mucosal layers of the same area, indicating that the muscular layer of the gastric corpus is the zone involved in this phenomenon. Pretreatment with the selective sensory neurotoxin capsaicin induced a gastric CGRP-li decrease in the corpus and forestomach. Ethanol (96%) did not further decrease gastric corpus CGRP-li in capsaicin-pretreated rats. These findings suggest that 96% ethanol induced a decrease of CGRP-li deriving from a capsaicin-sensitive pool and that CGRP may play a role in gastric ulcer pathogenesis of haemorrhagic lesions induced by concentrated ethanol.

Analysis of Variance↗
PubMed1992

Cysteamine induced-duodenal ulcers are associated with a selective depletion in gastric and duodenal calcitonin gene-related peptide-like immunoreactivity in rats.

We have measured the endogenous levels of gastric and duodenal calcitonin gene-related peptide (CGRP)-, neurokinin A (NKA)-, galanin-vasoactive intestinal polypeptide (VIP)- and neuropeptide Y (NPY)-like immunoreactivity (li) in relation to cysteamine-induced gastric lesions and duodenal ulcers in rats. CGRP-li but not NKA-, galanin-, VIP- or NPY-li was decreased in gastric and duodenal samples following a single ulcerogenic dose of cysteamine (900 mg/kg p.o.). Temporal relationships of this phenomenon showed that CGRP-li was selectively decreased (stomach 45%, duodenum 68% as compared to controls, respectively after 24 h) concomitantly to the formation of acute gastric lesions and duodenal ulcers. Animals bearing healed ulcers 12 days after cysteamine, had gastroduodenal CGRP-li similar to control values. Pretreatment with the selective sensory neurotoxin capsaicin decreased gastroduodenal CGRP-li but not NKA-, galanin-, VIP- or NPY-li, showing that CGRP might be considered a marker of the afferent innervation of the gastroduodenal tract. The residual gastroduodenal CGRP-li levels in capsaicin-pretreated animals were not decreased by cysteamine administration, indicating that the effect of cysteamine is restricted to a peptide pool of primary afferent origin. Duodenal CGRP-li is selectively decreased by the duodenal ulcerogen cysteamine during the acute phase of ulcers formation and might be among the local mediators which afford protection against the ulcerogenic stimuli.

Animals↗
PubMed1992

Capsaicin-like activity of N-ethylmaleimide in rat stomach.

1. N-Ethylmaleimide (NEM) and capsaicin induced a release of calcitonin gene-related peptide-like immunoreactivity (CGRP-li) in superfusates from rat gastric corpus. 2. The prior application of capsaicin completely blocked CGRP-li release by NEM while the exposure to NEM reduced the capsaicin-evoked CGRP-li outflow by about 51%. 3. These findings provide evidence that NEM might exert capsaicin-like activity in rat stomach and the release of CGRP-li from capsaicin-sensitive afferent fibres might influence the properties exerted by NEM in this tissue.

Animals↗
PubMed1991

Ruthenium red selectively antagonizes capsaicin-induced release of vasoactive intestinal polypeptide (VIP) from the human colon.

Ruthenium red (RR) is an inorganic dye that has shown to block the actions of capsaicin on primary sensory neurons in different animal models. The aim of this study was to assess whether RR is able to antagonize the release of vasoactive intestinal polypeptide (VIP) evoked by capsaicin in the human colon. Samples of descending colon were collected from patients undergoing colectomy for carcinoma of the colon. Tissue slices from the muscle of human colon were exposed to either 10 microM capsaicin or an isotonic high K+ medium (KCl 80 mM), in the absence or presence of 10 microM RR. Either capsaicin or high K+ produced a prompt release of VIP. RR (10 microM) completely antagonized the capsaicin-induced release of VIP from muscle of human colon. This effect was elective, since VIP release evoked by high K+ was unaffected by the presence of RR. These findings indicate that RR acts as a selective antagonist of capsaicin in human tissue and that the mechanism underlying peptide release by capsaicin is preserved across species. Multiple mechanisms leading to VIP release exist in the human colon.

Aged↗
PubMed1991

Decrease of duodenal calcitonin gene-related peptide- and substance P-like immunoreactivity in rat duodenal ulcers.

We have investigated the endogenous levels of duodenal calcitonin gene-related peptide- (CGRP) and Substance P- (SP) like immunoreactivity (li) following the induction of duodenal ulcers in rats. Using three duodenal ulcerogens, namely cysteamine, dulcerozine or mepirizole given in a single oral dose, a decrease of duodenal CGRP-li and SP-li was observed. Time-relationship studies of this phenomenon show that CGRP-li and SP-li were decreased concomitantly to the formation of gastroduodenal ulcers after the administration of cysteamine (900 mg/kg p.o.). Pretreatment with the selective sensory neurotoxin capsaicin induced CGRP-li decrease in the duodenum, which was not further decreased by an ulcerogenic dose of cysteamine, indicating that cysteamine induced a release of CGRP-li of capsaicin-sensitive origin. Otherwise duodenal SP-li was not sensitive to capsaicin pretreatment and its duodenal content decreased by cysteamine originates from an intrinsic source. Our observations indicate that CGRP and SP may play an important local role in duodenal ulcerogenesis.

Animals↗
PubMed1991

Differential effect on neuropeptide release of different concentrations of hydrogen ions on afferent and intrinsic neurons of the rat stomach.

In the muscle layer of the glandular portion of the rat stomach, in vivo capsaicin pretreatment markedly reduced calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) but did not affect substance P-like immunoreactivity (SP-LI). Accordingly, in vitro superfusion of slices of this tissue with capsaicin (10 mumol/L) released CGRP-LI but not SP-LI, whereas both neuropeptides were released by 80 mmol/L K+. Exposure to relatively low-pH (pH 6) physiological salt solution induced an increase in the CGRP-LI outflow that was reduced by 70% in a Ca(2+)-free medium and was completely abolished by a previous exposure to capsaicin. However, superfusion with pH-6 medium did not produce any detectable SP-LI release. After exposure to pH-6 medium, both capsaicin and high-K+ medium were still able to release a consistent quantity of CGRP-LI and SP-LI, respectively. Increased mucosal blood flow induced by acid back-diffusion is considered a protective mechanism against mucosal gastric lesion. The present findings suggest that hydrogen ions diffusing into the gastric wall may promote protective vasodilatation by activating the "efferent" function of capsaicin-sensitive nerves without affecting the secretory process of other intrinsic peptidergic neurons.

Animals↗
PubMed1991

Interactions between sialoadenectomy and capsaicin-sensitive afferent fibers on gastric acid secretion in rats.

In this study we have investigated the relative influence of capsaicin-sensitive afferents and sialoadenectomy on gastric acid secretion. Sialoadenectomized (SALX) rats showed a decrease in gastric acid secretion and an increase in gastric calcitonin gene-related peptide-like immunoreactivity (CGRP-li) as compared to sham-operated animals. Capsaicin pretreatment (50 + 100 mg kg-1 in two days) markedly decreased gastric CGRP-li in both sham and SALX-operated rats and increased acid concentration and output only in SALX animals. In this latter case the concomitant absence of two potent endogenous antisecretory agents (CGRP and epidermal growth factor; EGF) may contribute to the observed hypersecretion. Gastric content of vasoactive intestinal polypeptide (VIP)-li was unaffected in SALX and capsaicin-treated rats. Capsaicin-sensitive afferents and EGF contained in the salivary glands may interact in the regulation of the gastric acid secretion.

Analysis of Variance↗
PubMed1991

Capsaicin-induced release of neurokinin A from muscle and mucosa of gastric corpus: correlation with capsaicin-evoked release of calcitonin gene-related peptide.

It has been proposed that capsaicin-sensitive nerves might participate in a gastric defence mechanism, possibly via a local release of sensory neuropeptides. In this study, it was examined whether capsaicin might induce the release of neurokinin A (NKA), substance P (SP) and calcitonin gene-related peptide (CGRP) from different regions of rat stomach. Firstly, the tissue content of NKA-, SP- and CGRP-like immunoreactivity (LI) was measured in the fundus, in the corpus, in the muscle layer and in the mucosa of corpus of control rats and rats pre-treated with systemic capsaicin, s.c. (50 mg/kg as newborn). A large depletion (about 80%) of CGRP-LI following capsaicin treatment was observed in all regions examined, while no difference was observed for NKA-LI and SP-LI. NKA-LI, SP-LI and CGRP-LI release induced by capsaicin was measured in different regions of the rat stomach. Both in the gastric fundus and in the corpus, capsaicin (10 microM) produced a remarkable release of of CGRP-LI and NKA-LI, but not of SP-LI. A second administration of the drug had no longer effect, indicating desensitization. In the gastric corpus, the capsaicin-induced NKA-LI and CGRP-LI release was larger from the muscle layer than from the mucosa. The present findings provide neurochemical evidence that both NKA-LI and CGRP-LI are released from different regions of the rat stomach and both peptides should therefore be taken into account when considering the efferent function of capsaicin-sensitive primary afferents at gastric level.

Animals↗
PubMed1991

Enzyme immunoassay for tachykinin-like immunoreactivity in the guinea pig spinal cord.

A solid-phase enzyme immunoassay for quantitation of tachykinin-like immunoreactivity (TK-LI) is presented. Because the antiserum K-12 recognizes various tachykinins, such as neurokinin A (100%), kassinin (103%), eledoisin (51%), neurokinin B (18%), physalaemin (0.7%), and substance P (0.7%), the immunoreactivity detected in this enzyme immunoassay has been termed TK-LI. The assay was performed on 96-well microtiter plates coated with a mouse monoclonal second antibody. After preincubation of soluble neurokinin A or samples and K-12 antiserum for 3 h at room temperature, acetylcholinesterase-labelled neurokinin A was allowed to react overnight at 4 degrees C. Samples were finally incubated with Ellman's reagent for 2 h and the absorbance was measured at 414 nm. The threshold for detection of TK-LI was 2 fmol/well. TK-LI release from guinea pig dorsal spinal cord slices was evoked by capsaicin or high K+ medium. The capsaicin-evoked TK-LI release was increased in the presence of thiorphan, but not in that of captopril.

Acetylcholinesterase↗