Biomedical subjects

D Renzi

Publications and source records attributed to D Renzi.

At least 37 records · Page 2Linked to original sources

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↗

PubMed1991

Interleukin-1 beta and tumor necrosis factor-alpha induce gene expression and production of leukocyte chemotactic factors, colony-stimulating factors, and interleukin-6 in human mesangial cells.

The capacity of human cultured mesangial cells to produce soluble factors potentially relevant for mechanisms of inflammation and immunity at the glomerular site was analyzed. The nature of the secreted factors initially was investigated by Northern blot analysis using total cellular RNAs isolated from resting and activated mesangial cells. On exposure of mesangial cells to human recombinant interleukin-1 beta (IL-1 beta), high levels of interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) mRNAs were detected. Similar transcripts were found after stimulation with human recombinant tumor necrosis factor-alpha (TNF-alpha). Active secretion of IL-8 was documented by radioimmunoassay in supernatants of mesangial cells activated by either IL-1 beta or TNF-alpha. Using an in vitro migration assay, supernatants from resting mesangial cells were found to be devoid of any chemotactic activity for granulocytes or monocytes. On stimulation with IL-1 beta, however, mesangial cell supernatants expressed MCP-1 biologic activity detected as induction of a strong migratory response for human monocytes but not for granulocytes. In addition, IL-1 beta and TNF-alpha induced high levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) mRNAs. Similarly IL-1 beta and TNF-alpha induced the interleukin-6 (IL-6) gene and active secretion of its mature protein. These data strongly support an effector role for mesangial cells in modulating immune-inflammatory responses in glomeruli. Release of cytokines may activate not only infiltrating inflammatory cells through short paracrine pathways, but also mesangial cells themselves through an autocrine pathway.

Cells, Cultured↗

PubMed1990

Duodenal SP-like immunoreactivity is decreased in experimentally-induced duodenal ulcers.

Substance P-like immunoreactivity (SP-li) is decreased in duodenal samples of animals treated with a single dose of an ulcerogen such as dulcerozine, mepirizole or cysteamine. Unlike dulcerozine- or mepirizole-induced ulcers the degree of cysteamine-induced duodenal lesions is inversely correlated with the levels of duodenal SP-li. A significant decrease in duodenal SP-li was observed at 24 h, but not at 6 h after a single oral dose of cysteamine. These findings show that endogenous SP may play an important local role in duodenal ulcerogenesis.

Animals↗

PubMed1990

Motor response of the human isolated colon to capsaicin and its relationship to release of vasoactive intestinal polypeptide.

The aim of this study was to obtain indirect evidence of the presence of capsaicin-sensitive afferents in the human colon by studying the motor response to capsaicin of longitudinal strips from the human isolated taenia coli in parallel to the ability of capsaicin or KCl to induce peptide release from the human superfused colon. Capsaicin (1 microM) evoked a relaxation of the taenia, approaching 60-80% of the response to isoprenaline. Tachykinins evoked contractions of the taenia, while calcitonin gene-related peptide induced a relaxation. Neither tachyphylaxis to calcitonin gene-related peptide nor preincubation with an anti-calcitonin gene-related peptide serum did block the response to capsaicin which was also unaffected by tetrodotoxin, apamin, naloxone or an anti-galanin serum. Vasoactive intestinal polypeptide produced a concentration-dependent tetrodotoxin-resistant relaxation which was shifted rightward in the presence of anti-vasoactive intestinal polypeptide serum. The anti-vasoactive intestinal polypeptide serum reduced the response to capsaicin and application of capsaicin prevented the ability of anti-vasoactive intestinal polypeptide serum to block exogenous vasoactive intestinal polypeptide. Capsaicin (1 microM) evoked a significant release of vasoactive intestinal polypeptide-like immunoreactivity from the superfused muscle but not mucosa of the human colon. A significant vasoactive intestinal polypeptide-like immunoreactivity release was also observed in response to KCl (80 mM). KCl but not capsaicin evoked a significant release of neurokinin A-like immunoreactivity from colonic muscle and mucosa. No significant release of either substance P-, neuropeptide Y-, galanin- or calcitonin gene-related peptide-like immunoreactivity was detected in response to capsaicin or KCl although detectable levels of each peptide were evident in tissue extracts.(ABSTRACT TRUNCATED AT 250 WORDS)

Apamin↗

PubMed1990

Endothelin and eicosanoid synthesis in cultured mesangial cells.

We investigated the effect of endothelin on the generation of eicosanoids, which are known to regulate basal and stimulated mesangial cell tone. The results showed that endothelin is a potent stimulus of prostaglandin E2 (PGE2), prostacyclin (PGI2), and thromboxane A2 (TxA2) synthesis by bovine mesangial cells. Percentage increases in eicosanoid synthesis induced by endothelin (10(-10) to 10(-6) M), were 50 to 275% for PGE2, 28 to 168% for PGI2 and 42 to 111% for TxA2, respectively. Endothelin-induced eicosanoid synthesis in mesangial cells was concentration, but not time dependent. Aspirin (500 microM) completely prevented endothelin-induced eicosanoid synthesis. The calcium entry blocker nitrendipine (10(-8) M) failed to inhibit endothelin-induced eicosanoid synthesis. These data suggest that endothelin-induced changes in renal circulation and glomerular function in normal and disease conditions may be modulated by the concomitant stimulation of mesangial eicosanoid synthesis.

Animals↗

PubMed1990

Intraluminal release of PGE2 due to gastric perfusion of urethane-anaesthetized rats with hydrochloric or taurocholic acid.

We have measured the intragastric release of prostaglandin E2-like immunoreactivity (PGE2-li), pH changes and mucosal damage in response to gastric perfusion with hydrochloric or taurocholic acid at pH 1.5 in urethane-anaesthetized rats. Hydrochloric acid-perfusion caused a reversible decrease in pH values, no damage to the gastric mucosa and an intraluminal release of PGE2-li. Exposure to an ulcerogenic dose (25 mM) of taurocholic acid produced an intraluminal release of PGE2-li much higher than that of the non-ulcerogenic perfusion with hydrochloric acid. These findings indicate that intraluminal release of PGE2-li, thought to play a role as an endogenous antiulcer factor, can occur in response to a stimulus producing a significant damage of the gastric mucosa or to a mild irritant stimulus.

Anesthesia↗

PubMed1989

Effect of thiorphan on response of the guinea-pig gallbladder to tachykinins.

Tachykinins produced a concentration-related contraction of the isolated guinea-pig gallbladder, with a rank order of potency neurokinin A (NKA) greater than Arg-neurokinin B = neurokinin B (NKB) greater than substance P (SP). Only the effect of SP was potentiated by thiorphan (0.1-10 microM). A significant enhancement of the response to SP was also produced by captopril (1 microM). [Nle10]NKA-(4-10) and [beta-Ala8]NKA-(4-10), selective NK-2 receptor agonists, were active, whereas [Pro9]SP sulfone (selective NK-1 agonist) was almost ineffective. [MePhe7]NKB (selective NK-3 agonist) had some activity but only at high concentrations. Septide was almost ineffective and DiMeC7 had an action comparable to that of [MePhe7]NKB. None of the effects induced by these synthetic tachykinin analogs were significantly potentiated by thiorphan. Capsaicin (10 microM) produced a contraction which was unaffected by thiorphan. Both capsaicin and NKA-induced contractions were antagonized by Spantide at concentrations (5-10 microM) which had no effect against the atropine-sensitive contractions produced by electrical field stimulation. Capsaicin (1 microM) produced a consistent release of SP-like immunoreactivity (SP-LI) and a second application of the drug had no further effect, indicating complete desensitization. SP-LI release by capsaicin was almost doubled in the presence of thiorphan. These findings indicate that NK-2 and possibly some NK-3 receptors mediate the contractile response of the guinea-pig gallbladder to tachykinins. Both exogenous and endogenous (released by capsaicin) SP were degraded to a significant extent in this organ via a thiorphan-sensitive mechanism, the identity of which remains to be established.

Animals↗

PubMed1989

Duodenal ulcers are associated with a depletion of duodenal calcitonin gene-related peptide-like immunoreactivity in rats.

Calcitonin gene-related peptide-like immunoreactivity (CGRP-li) was decreased in duodenal samples from animals treated with ulcerogens such as dulcerozine, cysteamine or mepirizole. The degree of these experimental ulcers was inversely correlated with the levels of duodenal CGRP-li. These findings show that endogenous CGRP may play an important role in duodenal ulcerogenesis.

Animals↗

PubMed1989

Renal hemodynamic and natriuretic effects of human atrial natriuretic factor infusion in cirrhosis with ascites.

We investigated the effect of a continuous infusion (50 micrograms as an initial bolus followed by a maintenance infusion at a rate of 0.1 micrograms/min.kg body wt for 45 min) of synthetic human atrial natriuretic factor (hANF) on renal hemodynamics and the renin-angiotensin-aldosterone system in 15 cirrhotic patients with ascites. Basal hANF levels were higher in cirrhotic patients when compared with normal values. Human atrial natriuretic factor infusion induced a significant decrease in mean blood pressure (from 77.8 +/- 1.1 to 68.6 +/- 1.5 mmHg, p less than 0.001) and a significant increase in heart rate (from 76.4 +/- 2.7 to 89.8 +/- 2.4 beats/min, p less than 0.001) in the patients studied. A remarkable increase in natriuresis (i.e., greater than or equal to 200 muEq/min) was observed in 5 patients (responders), whereas the infusion did not modify sodium excretion (i.e., less than or equal to 20 muEq/min) in 6 patients (nonresponders) and induced an intermediate response in 4 patients. Human atrial natriuretic factor-induced natriuresis was related to changes in renal hemodynamics that occurred during hANF infusion. In responders, the extent of the natriuretic response paralleled the increase of effective renal plasma flow and glomerular filtration rate; in non-responders the absent natriuretic response was associated with an evident reduction of these parameters. The reduction of blood pressure was similar in responders and nonresponders, but in the latter group it was followed by a marked increase of plasma renin activity and heart rate. It is likely that in nonresponders the natriuretic effect of hANF was blunted by the hemodynamic and hormonal changes triggered by the concomitant hANF-induced hypotension. This probably occurs in the presence of a greater reduction of effective arterial blood volume, as suggested by the higher baseline levels of plasma renin activity and the inability to increase free water excretion after a water load observed in nonresponders.

Adult↗

PubMed1989

Release of substance P- and calcitonin gene-related peptide-like immunoreactivity and motor response of the isolated guinea pig gallbladder to capsaicin.

The aim of this study was to assess whether a local motor response to capsaicin could be observed in the isolated guinea pig gallbladder and to discover the mechanism involved. Capsaicin produced a contraction of this organ that exhibited desensitization, suggesting a specific action on sensory nerves. In preparations preexposed to capsaicin to produce a functional blockade of the capsaicin-sensitive sensory fibers, the contractile response to field stimulation was unaffected as compared with controls. Tachykinins (substance P and neurokinin A) produced a concentration-related contraction of this organ, neurokinin A being more potent than substance P. Spantide, a tachykinin antagonist, markedly inhibited the capsaicin-induced gallbladder contraction, leaving the atropine-sensitive response to field stimulation unaffected. Calcitonin gene-related peptide (CGRP) produced a concentration-related relaxation, which was tetrodotoxin-resistant, suggesting a direct effect on muscle cells. Repeated administration of CGRP produced desensitization. At this stage, application of capsaicin produced a contractile response much larger than in controls. Both substance P- and CGRP-like immunoreactivity were detected in the guinea pig gallbladder by radioimmunoassay and were significantly reduced after systemic capsaicin desensitization. Capsaicin induced the simultaneous release of substance P- and CGRP-like immunoreactivity from superfused isolated gallbladders. These findings indicate that capsaicin-sensitive nerves in the guinea pig gallbladder can produce a local motor response involving the release of multiple neuropeptides. In the guinea pig gallbladder, tachykinins and CGRP might act as "physiologic antagonists," as observed in other viscera from rats and guinea pigs.

Animals↗

PubMed1989

Interference of WEB 2086 and BN 52021 with Paf-induced effects on guinea-pig trachea.

1. The thienotriazolodiazepine WEB 2086 and the gingkolide BN52021 have been evaluated as antagonists of Paf-acether (Paf) by studying their effects on Paf-induced relaxation and Paf-induced prostaglandin E2 (PGE2) production in histamine-contracted guinea-pig tracheal preparations. 2. Relaxation induced by Paf 4 microM in histamine-contracted guinea-pig tracheal preparations was 39.67 +/- 3.5% (n = 30). At the same concentration, Paf significantly increased PGE2 production from histamine-contracted guinea-pig tracheal preparations. 3. WEB 2086 inhibited in a dose-related manner (IC50 = 21.2 nM) the relaxant effect induced by Paf and, at 1 microM, suppressed Paf-induced release of PGE2. 4. BN 52021 100 microM inhibited to about 60% Paf-induced relaxation of histamine-contracted guinea-pig tracheal preparations, but completely abolished Paf-induced increase in PGE2. 5. Both antagonists had no effects on relaxations induced by arachidonic acid 10 microM or PGE2 0.1-1 microM in histamine-contracted guinea-pig tracheal preparations. 6. The results are consistent with the presence of specific Paf receptors in guinea-pig trachea and indicate that a relaxant prostanoid, namely PGE2, at least partially mediates Paf-induced relaxation in this experimental model.

Animals↗

PubMed1988

A second antibody solid-phase enzyme immunoassay of prostaglandin E2 in human gastric juice.

A second antibody solid-phase enzyme immunoassay for the determination of prostaglandin E2 in human gastric juice was developed using acetylcholine esterase as label, covalently coupled to the eicosanoid. The assay was performed on 96-well microtiter plates coated with the second antibody (swine antirabbit IgG antibody). The enzyme-labeled and unlabeled prostaglandin E2 were allowed to react in a competitive manner with the immobilized specific antibody (rabbit anti-prostaglandin E2 serum). After addition of the enzyme substrate, the specifically bound acetylcholine esterase was determined at 414 nm by means of a colorimetric assay and the enzyme activity was correlated with the amount of unlabeled prostaglandin E2. According to the calibration curve, prostaglandin E2 was determined in the range of 0.5-250 pg/ml. The minimal detectable concentration of prostaglandin E2 was 1.9 +/- 0.2 pg/ml. The intraassay coefficient of variation was less than 10%. Most prostaglandins and their metabolites tested showed a cross-reactivity of less than 1%.

Chromatography, High Pressure Liquid↗