Biomedical subjects

L Bueno

Publications and source records attributed to L Bueno.

At least 19 recordsLinked to original sources

PubMed2000

Brain interleukin-1beta and tumor necrosis factor-alpha are involved in lipopolysaccharide-induced delayed rectal allodynia in awake rats.

Recently, we have developed a model of delayed (12 h) increase in sensitivity (allodynia) to rectal distension (RD) induced by intraperitoneal lipopolysaccharide (LPS) in awake rats. Thus, we examined whether central interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) are involved in LPS response. Abdominal contractions (criterion of visceral pain) were recorded in rats equipped with intramuscular electrodes. RDs were performed at various times after pharmacological treatments. RD induced abdominal contractions from a threshold volume of distension of 0.8 ml. At lowest volume (0.4 ml), this number was significantly increased 12 h after LPS. Intracerebroventricular (i.c.v.) injection of IL-1 receptor antagonist, IL-1beta converting enzyme inhibitor or recombinant human TNF-alpha soluble receptor reduced LPS-induced increase of abdominal contractions at 0.4 ml volume of distension. When injected i.c.v., recombinant human IL-1beta and recombinant bovine TNF-alpha reproduced LPS response at 9 and 12 h and at 6 and 9 h, respectively. These data suggest that IL-1beta and TNF-alpha act centrally to induce delayed rectal hypersensitivity and that central release of these cytokines is responsible of LPS-induced delayed (12 h) rectal allodynia.

Animals↗

PubMed1999

Vagally dependent protective action of calcitonin gene-related peptide on colitis.

This work evaluates the mechanism of action of calcitonin gene-related peptide (CGRP) on colitis. Firstly, Wistar rats were intracolonically instilled with trinitrobenzenesulfonic acid (TNBS) and i.v. treated by either alphaCGRP, or hCGRP(8-37), or by vehicle. The inflammatory level was evaluated 8 h and 4 days after TNBS. Secondly, intracerebroventricular alphaCGRP was assessed on the 4-day group with colitis. Finally, i.v. alphaCGRP was administered in vagotomized animals, and tested on the 4-day group with colitis. Colitis was aggravated by hCGRP(8-37), and decreased by peripheral but not central alphaCGRP. AlphaCGRP was inactive on inflammatory parameters in vagotomized colitic rats. This suggests that endogenous peripheral CGRP has an anti-inflammatory role in TNBS-induced colitis, depending upon the integrity of the vagus.

Animals↗

PubMed1999

Racecadotril demonstrates intestinal antisecretory activity in vivo.

BACKGROUND: Racecadotril (acetorphan), a potent enkephalinase inhibitor, protects endogenous enkephalins from degradation. Racecadotril exhibits experimental and clinical antidiarrhoeal activity without any effect on intestinal motility, suggesting selective antisecretory activity. The antisecretory effect of racecadotril was directly assessed in the present study. METHODS: A 1 m, jejunal, Thiry-Vella loop was created in six mongrel dogs, and water and ionic fluxes were evaluated during infusion (2 mL/min) of Tyrode solution labelled with 14C-polyethylene glycol. Fluxes were determined both in the basal state and 5-6 h after commencement of a 2-h infusion of cholera toxin (0.4 microgram/mL). Racecadotril (10 mg/kg) or vehicle was given orally with and without prior intravenous administration of naloxone (0.1 mg/kg) or phentolamine (0.2 mg/kg). RESULTS: Basal absorption remained unchanged following racecadotril administration; however, racecadotril significantly decreased (P = 0.01) cholera toxin-induced water, sodium, and potassium hypersecretion, from 0.73 +/- 0.15 to 0.37 +/- 0.13 mL/min; from 125.0 +/- 16.1 to 14.7 +/- 9.5 microMol/min; and from 3.41 +/- 0.66 to 1.66 +/- 0.61 microMol/min, respectively. This antisecretory activity of racecadotril was suppressed by naloxone but not by phentolamine. CONCLUSIONS: This study directly demonstrates the antisecretory activity of racecadotril in relation to the protection of endogenous enkephalins.

Animals↗

PubMed1999

Reduction of the nociceptive response to gastric distension by nitrate ingestion in rats.

BACKGROUND: Dietary nitrates are known to produce nitric oxide in the stomach, which may influence gastric function. AIM: To investigate whether nitrate ingestion modifies gastric sensitivity to distension through a mechanism involving nitric oxide production. METHODS: Nociception, associated with gastric distension ranging from 10 to 40 mmHg, was assessed in anaesthetized rats by the amplitude of cardiovascular depressor responses. Gastric volume corresponding to each distension was recorded. The following intragastric administrations (1 mL) were performed before distension: water (control), KNO3, NaNO3, KCl, NaCl (all at 0.1 mmol/kg), standard food (0.5 g), sodium nitroprusside, a nitric oxide donor (5 mg/kg), and haemoglobin, a nitric oxide scavenger (150 mg/kg) given either with water or KNO3. RESULTS: In controls, the fall in blood pressure increased from 7.8 +/- 2.0 to 31.6 +/- 2. 7 mmHg at distending pressures from 10 to 40 mmHg, respectively. KNO3 significantly reduced the amplitude of blood pressure response for the highest distending pressures (35 and 40 mmHg), while KCl induced a reduction in blood pressure response at all gastric pressures. NaNO3 and NaCl did not induce significant changes in distension-induced depressor responses. Administration of 0.5 g of standard food or sodium nitroprusside reproduced the effect of KNO3, which was reversed by haemoglobin. None of the compounds modified the gastric pressure-volume relationship, except KNO3, which increased gastric volume for the lowest distending pressures, and haemoglobin, which reduced the volume for the highest pressure. CONCLUSIONS: Ingestion of potassium nitrate reduces the sensitivity to gastric distension, through a mechanism involving nitric oxide.

Animals↗

PubMed1999

Influence of age on rectal tone and sensitivity to distension in healthy subjects.

Hypersensitivity to rectal distension is frequently observed in patients with irritable bowel syndrome (IBS). However, few data are available about the influence of age on rectal sensory thresholds and tone. The aim of this study was to measure rectal sensory thresholds and tone with a barostat in 12 healthy subjects (aged 86 +/- 4 years, eight females, four males) as compared with 12 young healthy male controls (26 +/- 1 years). Isobaric phasic distensions were performed in the fasted state (increment of 4 mmHg, steps of 5 min, interval of 5 min). Rectal tone changes were then measured as changes in volume of the barostat bag, the pressure being kept constant. After a baseline recording of 1 h, a 1000-kcal meal was served and the tone recorded until return to baseline. Rectal sensory thresholds were significantly higher in aged subjects. First sensation, sensation of urge to defaecate and sensation of pain were triggered at 21.1 +/- 3.2 mmHg, 30.4 +/- 5.4 mmHg and 40.5 +/- 5.0 mmHg, respectively, in aged subjects, vs 13.3 +/- 4.6 mmHg (P < 0.05), 20.7 +/- 1.0 mmHg (P < 0.001) 31.3 +/- 1.7 mmHg (P < 0.001) in controls. Rectal compliance was not significantly different between the two groups. Mean barostat bag volume was 104 +/- 13 mL in fasting aged subjects and 125 +/- 23 mL in controls (NS). After the meal, the barostat bag volume decreased by 69 +/- 11% during 85 +/- 17 min in aged subjects and 75 +/- 14% during 89 +/- 15 min in young controls (NS). Rectal sensory thresholds triggered by distension are increased in aged healthy subjects while compliance and tone are not different. Age should be considered as a confounding factor when studying rectal sensitivity and further studies in aged patients with IBS should include a group of control subjects within the same range of age as studied patients.

Adult↗

PubMed1999

Involvement of tachykinin receptors in sensitisation to cow's milk proteins in guinea pigs.

BACKGROUND: There is growing evidence for a pivotal role for tachykinins in gut neuroimmune interactions. AIMS: To determine whether NK1, NK2, and NK3 tachykinin receptors are involved in milk protein induced allergic sensitisation. METHODS: Eight groups of 12 Dunkin-Hartley guinea pigs (250-300 g) were used. Four groups were sensitised to milk proteins for three weeks. During this period, these animals were injected intraperitoneally each day with NK1 (SR 140333; 0.3 mg/kg), NK2 (SR 48968; 5 mg/kg), or NK3 (SR 142801; 5 mg/kg) receptor antagonist or vehicle. The fifth group had water available instead of milk and was used as a non-sensitised control. The three other groups received the NK receptor antagonists for three weeks but were not sensitised to milk proteins. RESULTS: Sensitised animals treated with NK1 and NK3 receptor antagonists had both lower IgE and IgG serum titres, evaluated by passive cutaneous anaphylaxis, and lower specific IgG serum titres, determined by enzyme linked immunosorbent assay (ELISA), than vehicle treated animals. Sensitisation induced an increase in intestinal mast cell number which was abolished by treatment with the NK1 receptor antagonist. Antigenic challenge-induced jejunal hypersecretion was also blocked by treatment with the NK1 receptor antagonist. CONCLUSION: In guinea pigs, NK1 and NK3 but not NK2 receptors are involved in sensitisation to cow's milk. However, NK1 but not NK3 receptor antagonists abolish both the hypermastocytosis induced by food allergy and the hypersecretion induced by antigenic challenge, suggesting different roles for NK1 and NK3 receptors in the mechanisms of sensitisation to beta-lactoglobulin.

Animals↗

PubMed1999

Effects of inflammatory mediators on gut sensitivity.

Over the past decade, attention has been paid to the role of visceral sensitivity in the pathophysiology of functional bowel disorders, especially irritable bowel syndrome, and visceral hypersensitivity is the most widely accepted mechanism responsible for both motor alterations and abdominal pain. Inflammatory mediators sensitize primary afferents, especially C-fibre polymodal nociceptors, favouring the recruitment of silent nociceptors that give rise to secondary spinal sensitization. After local tissue injury, the release of chemical mediators such as potassium ions, ATP, bradykinin and prostaglandin E2 directly activate nerve endings and indirectly trigger the release of algesic mediators such as histamine, 5-hydroxytryptamine and nerve growth factor from other cells, which, in turn, stimulate proximal afferent nerve endings and silent nociceptors. Among the intermediary structures activated by inflammatory mediators and susceptible to the release of proalgesic substances, mast cells and platelets play a crucial role; however, immunocytes such as macrophages and neutrophils or sympathetic nerve terminals are also candidates. Moreover, events likely to activate synthesis of mediators by mast cells, such as stress and septic shock, also trigger colonic hypersensitivity. Prolonged visceral hyperalgesia may also depend on spinal sensitization. A number of substances are candidates to play a role at the spinal cord level in mediating painful and nonpainful sensations. Among them, substance P, dynorphins and glutamate play a pivotal role in postsynaptic sensitization, particularly during and after gut inflammation. Finally, despite the complexity of the relationship between inflammatory mediators and gut hypersensitivity, numerous results strongly suggest that alteration neuroimmune communications at the gut level may trigger a series of events that give rise to chronic changes in visceral sensitivity.

Adenosine Triphosphate↗

PubMed1999

New and future drugs in nerve-gut dysfunction.

There is increasing evidence that modifications in brain-gut communications are responsible for the occurrence of Functional Bowel Disorders. Based on various experimental models of modified gut sensitivity and the emergence of new pharmacological tools, it is now possible to identify new targets for the corrections of altered brain-gut communications and to improve our understanding of functional gastrointestinal disorders. Both local inflammatory related components and central nervous system acting factors are associated to trigger dysfunctioning and neuropeptides such as tachykinins, bradykinin and calcitonin gene-related peptide are involved in peripheral and spinal sensitization of afferent neurons. Serotonin released from entero chromaffin cells, mast cells, platelets or nerves also play a role, through different receptor subtypes, in initiating gut hypersensitivity. Brain modulation of impaired ascending messages also appears to be an important approach for the correction of symptoms related to gut hyper-responsiveness.

Animals↗

PubMed1998

Protective role of vagal afferents in experimentally-induced colitis in rats.

The aim of this study was to evaluate the regulatory role of vagal afferents in the development of colonic inflammation induced by trinitrobenzenesulfonic acid (TNBS) in rats. Groups of Wistar rats were treated with capsaicin or its vehicle applied perivagally (sham treatment). Colonic transit time was evaluated, and, two days later, one half of the animals received an intracolonic instillation of TNBS/ethanol (40 mg/kg), and the other received saline. Inflammation was evaluated functionally (gut permeability), biochemically (myeloperoxydase activity) and histologically. Vagal capsaicin deafferentation did not modify colonic transit time. In TNBS treated groups, inflammation was enhanced by capsaicin pretreatment, as determined by an increased gut permeability, MPO activity, and histological damage score. These results suggest that vagal afferents have a protective role in TNBS-induced colitis in rats, unrelated to changes in colonic transit time.

Animals↗

PubMed1998

Involvement of interleukin-1, prostaglandins and mast cells in rectal distension-induced colonic water secretion in rats.

1. In vivo rectal distension (RD) induces a neurally mediated colonic net water hypersecretion in rats. Interleukin-1 beta (IL-1 beta) also induces neural colonic water hypersecretion involving the release of prostaglandins (PGs) and a mast cell degranulation in rats. This study investigated in vivo the role of IL-1, PGs and mast cells in RD-induced colonic hypersecretion. 2. Proximal colonic net water flux was determined using [14C]polyethylene glycol (PEG) 4000 (mol. wt. 4000) in anaesthetized rats. On strips taken from the distal colon: (i) a histological analysis was performed to determine the number of mucosal mast cells (MMC); and (ii) histamine levels were measured by radioimmunoassay after stimulation with compound 48/80. 3. RD induced a net colonic water secretion that was blocked by i.c.v. administration of IL-1ra (an IL-1 receptor antagonist) and indomethacin, and by systemic treatment with doxantrazole and indomethacin. RD decreased the number of resident mast cells and the release of histamine from the distal colonic strips. Moreover, using SDS-PAGE immunoblotting the expression of IL-1 beta was detected in the brain. 4. These results suggest that, in rats, RD induces colonic net water hypersecretion by the activation of a neuro-immunological reflex pathway, involving IL-1 beta, PG release and peripheral mast cell degranulation.

Animals↗

PubMed1998

Low-level exposure to diquat induces a neurally mediated intestinal hypersecretion in rats: involvement of nitric oxide and mast cells.

Diquat, a nonselective desiccant herbicide, induces a significant secretion of fluid into the lumen of the gastrointestinal tract of rats at sublethal doses (from 0.5 to 50 mg/kg). This study investigated the effect of an acute low-level exposure to diquat (0. 1, 0.5, and 1 mg/kg) on intestinal net water flux and the mechanisms involved. In anesthetized rats, an intestinal loop (7 cm) was infused with Ringer's buffer containing [14C]-polyethylene glycol 4000. After equilibration, diquat (0.1, 0.5, and 1 mg/kg) was added to Ringer's buffer during 60 min. Net water flux was calculated according to [14C] activity determined in the effluent collected at 15-min intervals. Infused in the intestinal loop for 60 min at doses of 0.5 and 1 mg/kg but not at 0.1 mg/kg, diquat induced an intestinal net water secretion during 180 min with a maximal effect at the highest dose used and during the first hour following the end of diquat infusion. Diquat-induced (1 mg/kg) intestinal net water secretion was blocked by a neurotoxin, tetrodotoxin (5 micrograms/kg iv), doxantrazole (5 mg/kg ip), a mast cell stabilizer, and two inhibitors of NO synthases: l-NAME (25 mg/kg ip) and aminoguanidine (2 mg/kg ip). It is concluded that a single low-level (0.5 and 1 mg/kg) intrajejunal administration of diquat induces a net water intestinal secretion and that this secretory effect is nerve-mediated, implying mast cell degranulation and NO release.

Animals↗

PubMed1998

Comparative effects of nonpeptide tachykinin receptor antagonists on experimental gut inflammation in rats and guinea-pigs.

Previous studies have shown tachykinins implicated in gut inflammation. The aim of this work was to evaluate the effect of treatments with tachykinin NK1, NK2, and NK3 selective receptor antagonists on the development of gut inflammation induced by trinitrobenzenesulfonic acid (TNBS) in rats and guinea-pigs. On day 0, rats and guinea-pigs received an intraluminal instillation of TNBS/ethanol (40 mg/kg). Each group was daily treated with intraperitoneally injected NK1 (SR 140333; 0.3 mg/kg/day), NK2 (SR 48968; 5 mg/kg/day), or NK3 (SR 142801; 1, 5, or 10 mg/kg/day) receptor antagonists or their vehicle. On day 4, inflammatory levels were evaluated by measuring gut permeability, myeloperoxidase activity, macro- and microscopic damage scores. In TNBS treated rats, daily administration of SR 140333 (0.3 mg/kg/day) and SR 48968 (5 mg/kg/day) reduced colonic inflammation. In TNBS treated guinea-pigs, daily administration of SR 48968 (5 mg/kg/day) and SR 142801 (at 5 and 10 mg/kg/day) attenuated significantly ileal injury. These results suggest that non-peptide tachykinin receptor antagonists are potent anti-inflammatory agents on gut inflammation in rats and guinea-pigs. However, their activity depends upon the animal species and type of receptor considered.

Animals↗

PubMed1998

Effect of sorbin derivatives on cholera toxin-induced intestinal secretion in rat in vivo.

The effect of synthetic sorbin derivatives was determined on cholera toxin-stimulated jejunal secretion in anesthetized rats in vivo, using both perfused and ligated loop. An inhibitory effect on water secretion induced by cholera toxin was shown with C-terminal sorbin peptides: C20 (YEPGKSSILQHERPVTKPQA-amide), C10 and Dala 7 heptapeptide-amide of sorbin, given by subcutaneous (SC) or intraduodenal administration. When perfused intravenously, C20-sorbin inhibited the cholera-induced stimulation of net flux of water, Na+ and K+, in the jejunum and at the same time the net flux of water and Cl- in the duodenum, which was not in contact with the toxin. 5-hydroxytryptamine was not significantly changed in plasma or fluid. Prostaglandin E2 release in jejunal as well as duodenal fluid was significantly stimulated by cholera toxin, but was not significantly different from basal value after C20 administration.

Amino Acid Sequence↗

PubMed1998

Mast cell degranulation induces delayed rectal allodynia in rats: role of histamine and 5-HT.

Visceral hypersensitivity is a common feature of functional bowel disorders, where an increased number of mast cells have often been described. Thus, we investigated the effect of an experimental mast cell degranulation induced by BrX-537A on somatic (tail heating) and visceral (rectal distension) sensitivity in rats and the involvement of histamine and/or serotonin on this last response. After BrX-537A administration, the latency of tail withdrawal reflex was shortened within the 2- to 8-hr period. Moreover, BrX-537A reduced the distension volume threshold from 0.8 ml to 0.4 ml inducing allodynia, from 6 to 12 hr after its administration. This effect was suppressed by doxantrazole (mast cell stabilizing agent) and WAY 100635 (5-HT1A receptor antagonist), and reproduced by 5-HTP (5-HT precursor) and 8-OH-DPAT (5-HT1A receptor agonist). However, neither granisetron (5-HT3 receptor antagonist) nor H1, H2, or H3 histamine receptor antagonists modified the BrX-537A-induced allodynia. Consequently, mast cell degranulation initiates a delayed somatic and visceral allodynia, with the participation of serotonin, through 5-HT1A receptor activation, on the visceral response.

Animals↗

PubMed1998

Decrease in gastric sensitivity to distension by 5-HT1A receptor agonists in rats.

Using an in vivo model for evaluation of gastric sensitivity in awake rats, we aimed to determine whether 5-hydroxytryptamine 1A (5-HT1A) agonists modify pain threshold and gastric compliance specifically through 5-HT1A receptors. Isobaric gastric distensions were performed with a barostat using steps of 5 mm Hg in male rats equipped with a gastric balloon and electrodes implanted in the neck muscles. Gastric distension at 15 or 20 mm Hg induced a typical posture associated with contractions of the neck muscles. Rats received drugs 30 min before gastric distension. The 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), administered intraperitoneally (0.5 mg/kg) increased gastric pain threshold and gastric tone. These effects were reproduced when administered centrally (0.05 mg/kg) and blocked by intracerebroventricular administration of the 5-HT1A antagonist WAY 100635. Flesinoxan (4 mg/kg, intraperitoneally), another 5-HT1A agonist reproduced the effects of 8-OH-DPAT on pain threshold and gastric tone and the alpha2-receptor antagonist yohimbine did not modify the action of 8-OH-DPAT. Our results indicate that activation of 5-HT1A receptors at the level of the central nervous system increases gastric tone and decreases gastric sensitivity to distension.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1998

A model for evaluation of gastric sensitivity in awake rats.

We developed a model for the evaluation of gastric sensitivity to distension in awake rats. A balloon made from a latex condom was chronically placed in the stomach and three stainless steel electrodes were implanted in the neck muscles. Isobaric distensions were performed with a barostat by step of 5 mmHg with 10 min inflation and 2 min deflation. Gastric pressure, integrated neck electromyogram (EMG) and gastric volume were continuously monitored on a potentiometric recorder. Gastric distension at 15 or 20 mmHg induced a typical posture associated with contractions of the neck muscles. Pain threshold was defined as the pressure inducing an increase of integrated neck EMG greater than 100%. The mean pain threshold was 18.5 +/- 0.7 mmHg and was not modified 2, 4 and 7 days after the first experiment. However, gastric volumes were significantly higher on the 4th and the 7th days. Morphine at the doses of 0.4 and 4 mg kg-1 i.p. significantly increases the pain threshold. At the doses of 0.04 and 0.4 mg kg-1, morphine significantly increased gastric volume for the distending pressure of 10 mmHg. Naloxone (2.5 mg kg-1 i.p.) reversed the effects of morphine. In conclusion, our model permits simultaneous evaluation of pain threshold and gastric compliance associated with gastric distension in conscious rats.

Animals↗

PubMed1998

Intracolonic glycerol induces abdominal contractions in rats: role of 5-HT3 receptors.

Serotonin and 5-HT3 receptors may be involved in the activation of nociceptive afferent pathways by rectal distension. In rats, intracolonic infusion of glycerol is able to trigger nociceptive inputs as evidenced by the occurrence of abdominal constrictions. This work was designed to evaluate the influence of 5-HT3 receptor antagonists on this reflex and to approach the site of action by comparing their relative efficacies according to the route of administration. Male Wistar rats (250-350 g) were surgically prepared for abdominal electromyography and a catheter was placed in the colonic lumen. Five days after surgery, electrical activity of abdominal muscles was recorded before and during (20 min) intracolonic infusion of glycerol (60% glycerol + 40% saline, rate 0.75 mL/h). Cilansetron was administered intraperitoneally, 15 min before glycerol infusion, at doses of 5 to 500 micrograms/kg. Granisetron, ondansetron and cilansetron were administered at the dose of 20 micrograms/kg by intraperitoneal (i.p.), intravenous (i.v.) or intracolonic (i.c.) routes. The number of abdominal spike bursts was used as an index of visceral nociception. Intracolonic infusion of glycerol increased significantly (P < 0.05) the number of abdominal spike bursts during the time of infusion compared with saline (30.6 +/- 6.6 vs 4.5 +/- 3.4 bursts). When administered i.p., cilansetron dose-dependently reduced the frequency of abdominal spike bursts from the dose of 20 micrograms/kg i.p. Administration i.p. of granisetron and ondansetron at this dose also significantly reduced the number of abdominal spikes (19.0 +/- 6.0 and 18.3 +/- 6.9 respectively). Cilansetron, ondansetron and granisetron were also effective by i.v. and i.c. routes, cilansetron was more active by the i.c. route. Serotonin, via 5-HT3 receptors, is involved in the mediation of abdominal contractions induced by intracolonic infusion of glycerol. 5-HT3 receptor antagonists are also active by i.c. route suggesting a local site of action.

Animals↗

PubMed1998

Correlation of desensitisation of platelet activating factor (PAF) receptors with intensity of inflammation and intestinal PAF content during experimental ileitis in guinea pig.

AIM: To determine the kinetics of platelet activating factor (PAF) and prostaglandin E2 (PGE2) receptor desensitisation during intestinal inflammation induced by trinitrobenzenesulphonic acid (TNB) instillation and to study the relation between receptor regulation, inflammatory lesions, and PAF content of the gut wall. METHODS: Receptor desensitisation was assessed on isolated smooth muscle cells from the circular layer. PAF content of the intestinal wall was determined by thin layer chromatography and radioimmunoassay. RESULTS: After an acute inflammatory phase on day 1, subacute changes appeared in TNB instilled ileum, with a maximal intensity on day 6. In control animals, PAF 10 nM and PGE2 10 nM provoked a maximal contraction in the range of 24% of cell shortening. On days 1 and 3 after intestinal instillation of TNB, PAF induced contraction was not altered whereas the effect of PGE2 was progressively desensitised (2 logM rightward shift of its concentration-response curve: Cmax = 1 microM; p < 0.01). Between days 4 and 6, the concentration-response curve of PGE2 shifted by only 1 logM (p < 0.05) whereas the curve of PAF induced contraction shifted by 2 logM (Cmax = 1 microM; p < 0.01). The PAF content of the ileal wall was maximal between days 3 and 5 (300 ng/mg tissue). On days 10 and 15, PAF and PGE2 induced contractions were similar to those observed on day 1, and PAF content returned to basal. CONCLUSION: Inflammation induced by TNB instillation triggers PAF and PGE2 receptor desensitisation; this is dependent on the duration of inflammation and correlates with PAF content in the ileum. This receptor desensitisation may play a protective role by preventing overstimulation of intestinal smooth muscle cells.

Acetylcholine↗