Biomedical subjects

N M Griffiths

Publications and source records attributed to N M Griffiths.

At least 19 recordsLinked to original sources

PubMed2004

Persistence of altered 5-hydroxytryptamine turnover following hemibody X-irradiation in the rat distal colon.

PURPOSE: Acute gastrointestinal responses to ionizing radiation exposure include a role for 5-hydroxytryptamine (5-HT), but it is not known whether involvement of 5-HT persists and contributes to late effects. The aim was to investigate the acute and later effects of lower hemibody irradiation on 5-HT turnover and the biological effect in the rat distal colon. MATERIALS AND METHODS: Rats were exposed to 10 Gy lower hemibody X-radiation. 5-HT and 5-hydroxyindole acetic acid tissue levels were measured in the distal colon along with the serotonin re-uptake transporter and tryptophan hydroxylase mRNA. 5-HT-containing cells and crypt cell numbers were estimated in addition to 5-HT-stimulated short-circuit current responses in isolated mucosa. Studies were performed from 3 days to 3 months post-exposure. RESULTS: During the acute phase, at 3 days post-irradiation, reductions in cell number, tissue resistance, serotonin re-uptake transporter expression and secretory responses to 5-HT were observed. However, at later times when secretory responses were normal, 5-HT tissue levels and enterochromaffin cell numbers were increased. CONCLUSIONS: The results provide evidence that after 10 Gy hemibody irradiation, modifications persist past the acute phase. In particular, 5-HT turnover in the distal colon is altered during a longer period.

Animals↗

PubMed2004

Functional and structural alterations of epithelial barrier properties of rat ileum following X-irradiation.

Irradiation of the digestive system leads to alterations of the small intestine. We have characterized the disruption of the barrier integrity in rat ileum from 1 to 14 days following irradiation ranging from 6 to 12 Gy. The intestinal permeability to 14C-mannitol and 3H-dextran 70 000 was measured in vitro in Ussing chambers. In parallel to these functional studies, immunohistochemical analyses of junctional proteins (ZO-1 and beta-catenin) of ileal epithelium were performed by confocal microscopy. Irradiation with 10 Gy induced a marked decrease in epithelial tissue resistance at three days and a fivefold increase in mannitol permeability, without modifications of dextran permeability. A disorganization of the localization for ZO-1 and beta-catenin was also observed. At 7 days after irradiation, we observed a recovery of the organization of junctional proteins in parallel to a return of intestinal permeability to control value. In addition to these time-dependent effects, a gradual effect on epithelial integrity of the radiation doses was observed 3 days after irradiation. This study shows a disruption of the integrity of the intestinal barrier in rat ileum following abdominal X-irradiation, depending on the time postirradiation and on the delivered dose. The loss of barrier integrity was characterized by a disorganization of proteins of tight and adherent junctions, leading to increased intestinal permeability to mannitol.

Animals↗

PubMed2004

Screening of a large panel of gastrointestinal peptide plasma levels is not adapted for the evaluation of digestive damage following irradiation.

The aim of this study was to assess the potential of gastrointestinal peptide plasma levels as biomarkers of radiation-induced digestive tract damage. To this end, plasma levels of substance P, GRP, motilin, PYY, somatostatin-28, gastrin, and neurotensin were followed for up to 5 days in pigs after a 16-Gy whole-body X-irradiation, completed by a histopathological study performed at 5 days. Each peptide gave a specific response to irradiation. The plasma levels of GRP and substance P were not modified by irradiation exposure; neither were those of motilin and PYY. Concerning gastrin, a 2-3-fold increase of plasma concentration was observed in pig, which presented the most important histological alterations of the stomach. The plasma levels of somatostatin, unchanged from 1 to 4 days after irradiation, was also increased by 130% at 5 days. In contrast, a diminution of neurotensin plasma levels was noted, firstly at 1 day (-88%), and from 3 days after exposure (-50%). The present study suggested that changes in gastrin and neurotensin plasma levels were associated with structural alterations of the stomach and ileum, respectively, indicating that they may be relevant biological indicators of radiation-induced digestive damage to these segments.

Animals↗

PubMed2004

Alteration of the enterohepatic recirculation of bile acids in rats after exposure to ionizing radiation.

The aim of this work was to study acute alterations of the enterohepatic recirculation (EHR) of bile acids 3 days after an 8-Gy radiation exposure in vivo in the rat by a washout technique. Using this technique in association with HPLC analysis, the EHR of the major individual bile acids was determined in control and irradiated animals. Ex vivo ileal taurocholate absorption was also studied in Ussing chambers. Major hepatic enzyme activities involved in bile acid synthesis were also measured. Measurements of bile acid intestinal content and intestinal absorption efficiency calculation from washout showed reduced intestinal absorption with significant differences from one bile acid to another: absorption of taurocholate and tauromuricholate was decreased, whereas absorption of the more hydrophobic taurochenodeoxycholate was increased, suggesting that intestinal passive diffusion was enhanced, whereas ileal active transport might be reduced. Basal hepatic secretion was increased only for taurocholate, in accordance with the marked increase of CYP8B1 activity in the liver. The results are clearly demonstrate that concomitantly with radiation-induced intestinal bile acid malabsorption, hepatic bile acid synthesis and secretion are also changed. A current working model for pathophysiological changes in enterohepatic recycling after irradiation is thus proposed.

Animals↗

PubMed2004

Differential qualitative and temporal changes in the response of the hypothalamus-pituitary-adrenal axis in rats after localized or total-body irradiation.

Stress such as exposure to ionizing radiation is able to activate the hypothalamus-pituitary-adrenal axis. The present study sought to examine the effects of different configurations of a 10-Gy gamma irradiation in rats on the hypothalamus-pituitary-adrenal axis to understand the mechanism of negative feedback by glucocorticoids induced by ionizing radiation. Specifically, we determined adrenocorticotropin and corticosterone levels in plasma as well as corticotrophin-releasing factor expression in the paraventricular nucleus of the hypothalamus by in situ hybridization from 6 h to 4 days after total-body, abdominal or head irradiation. In this study, we found an activation of the hypothalamus-pituitary-adrenal axis after radiation exposure. Plasma adrenocorticotropin and corticosterone levels were significantly increased after total-body and abdominal irradiation 3 days after exposure, in parallel with decreased labeling of corticotrophin-releasing factor mRNA in the parvocellular region of the paraventricular nucleus of the hypothalamus. Our results suggest that ionizing radiation activates the neuroendocrine system to protect the organism from the occurrence of radiation-induced inflammation.

Adaptation, Physiological↗

PubMed2003

'In-field' and 'out-of-field' functional impairment during subacute and chronic phases of experimental radiation enteropathy in the rat.

PURPOSE: To investigate subacute and chronic functional consequences of localized irradiation of rat small intestine on exposed and shielded segments (proximal and distal). MATERIALS AND METHODS: The surgical model of a scrotal hernia was used. The ileal loop was exposed to single doses of 18, 21 or 29.6 Gy X-irradiation. Epithelial structure and transport capacity were followed 2 and 26 weeks post-exposure. RESULTS: Irradiated segments showed mucosal ulceration followed by transmural fibrosis. Transport capacity was impaired from 2 to 26 weeks. Subacute functional impairment was noticed in the proximal segment, without either morphological alteration or neutrophil influx. At 26 weeks, both proximal and distal segments showed impaired epithelial transport capacity, with neutrophil influx in the submucosa in cases of 21-Gy exposure and in the submucosa and muscularis propria after 29.6 Gy. CONCLUSIONS: Radiation enteritis was characterized by functional impairment, within as well as outside, the irradiation field. During the subacute phase, the irradiated segment may be a source of mediators which might influence intestinal function outside the site of injury via the blood stream and/or enteric nervous system. The development of an intestinal occlusion syndrome during the chronic phase might be responsible for intestinal dysfunction but it does not rule out a possible inflammatory process developing in the shielded parts of the small intestine.

Animals↗

PubMed2003

Effect of radiation on cAMP, cGMP and Ca(2+)(i) pathways and their interactions in rat distal colon.

The secretory response implicated in the intestinal response to luminal attack is altered by radiation. The cAMP, cGMP and Ca(2+)(i) pathways leading to secretion as well as the interactions between the cAMP pathway and the cGMP or Ca(2+)(i) pathway were studied in the rat distal colon 4 days after a 9-Gy abdominal X irradiation, when modifications mainly occurred. The secretory response in Ussing chambers and cAMP and cGMP accumulation in single isolated crypts were measured. The muscarinic receptor characteristics were determined in mucosal membrane preparations. The secretory response by the cAMP pathway (stimulated by vasoactive intestinal peptide or forskolin) and the cAMP accumulation in crypts were decreased (P < 0.05) after irradiation. The weak secretory response induced by the cGMP pathway (stimulated by nitric oxide or guanylin) was unaltered by radiation, and the small amount of cGMP determined in isolated crypts from the control group became undetectable in the irradiated group. Inducible NOS was not involved in the hyporesponsiveness to VIP after irradiation (there was no effect of an iNOS inhibitor). The secretory response by the Ca(2+)(i) pathway (stimulated by carbachol) was unaffected despite a decreased number and increased affinity of muscarinic receptors. The non-additivity of VIP and carbachol co-stimulated responses was unmodified. In contrast, VIP and SNP co-stimulation showed that NO enhanced the radiation-induced hyporesponsiveness to VIP through a reduced accumulation of cAMP in crypts. This study provides further understanding of the effect of ionizing radiation on the intracellular signaling pathways.

Animals↗

PubMed2002

Effect of granisetron on radiation-induced alterations of colonic motility and fluid absorption in rats.

BACKGROUND: Radiation-induced diarrhoea is attributed to both mucosal injury and alterations of intestinal motility. Previous reports have indicated that 5-hydroxytryptamine is released following irradiation, which may contribute to these changes. AIMS: To investigate the effects of granisetron (5-hydroxytryptamine type-3 receptor antagonist) on colonic motility, fluid absorption and 5-hydroxytryptamine colonic content following abdominal irradiation (10 Gy) in rats. METHODS: In vivo measurements of motility and fluid absorption in the proximal and distal colon, respectively, diarrhoea score and 5-hydroxytryptamine tissue levels were performed 3 and 7 days after abdominal irradiation. The effects of post-irradiation granisetron (0.3 mg/kg subcutaneously) were also evaluated. RESULTS: Colonic motility and fluid/Na(+) absorption were reduced 3 and 7 days after irradiation. All rats developed diarrhoea (3 days) concomitant with increased colonic mucosal 5-hydroxytryptamine levels. Granisetron prevented diarrhoea, attenuated decreased colonic motility and reduced 5-hydroxytryptamine levels on day 3, although fluid absorption was only slightly improved. On day 7, colonic motility and fluid/Na(+) absorption were restored in granisetron-dosed animals. CONCLUSIONS: These results indicate that radiation-induced diarrhoea involves alterations of both colonic motility and fluid/Na(+) absorption. 5-Hydroxytryptamine could be one of the mediators implicated in these alterations, as post-irradiation dosage with a 5-hydroxytryptamine type-3 receptor antagonist improved colonic motility and prevented diarrhoea on day 3.

Animals↗

PubMed2002

Dose dependence effects of ionizing radiation on bile acid metabolism in the rat.

PURPOSE: To study radiation dose-related changes of individual or total bile acids in various physiological fluids in order to identify potential bio-indicators of radiation-induced gastrointestinal injuries. MATERIALS AND METHODS: Wistar rats were sham- or whole-body gamma irradiated (1-12Gy). Total and individual bile acids were quantified, 3 days after exposure, in bile collected after catheterization of the bile duct. Total bile acid concentrations were also measured in plasma and colonic contents 1, 2 and 3 days after irradiation. These concentrations were determined by an enzymatic method whereas individual bile acids were quantified by HPLC. RESULTS: In bile, whereas total bile acid concentration remained unchanged after irradiation whatever the dose, the proportion of dihydroxy bile acids in the pool of total bile acids was gradually increased with the irradiation dose, especially from 8 Gy. In plasma samples, total bile acid concentrations fell for doses higher than 10 Gy. In colonic contents, bile acid concentrations increased progressively with time (from 1 to 3 days) and with irradiation dose (from 1 to 12Gy), reaching a plateau 3 days after exposure for doses higher than 10 Gy. CONCLUSIONS: These results show that changes in colonic bile acid concentrations which are reflected in faeces are perhaps a useful parameter to improve diagnosis and prognosis of radiation-induced gastrointestinal damage since it probably reflects directly intestinal bile acid malabsorption.

Animals↗

PubMed2002

Alterations in water and electrolyte absorption in the rat colon following neutron irradiation: influence of neutron component and irradiation dose.

PURPOSE: To study the absorptive function of rat colon following whole-body exposure to neutron irradiation, either to the same total dose with varying proportion of neutrons or to the same neutron proportion with an increasing irradiation dose. MATERIALS AND METHODS: Different proportions of neutron irradiation were produced from the reactor SILENE using a fissile solution of uranium nitrate (8, 47 and 87% neutron). Water and electrolyte fluxes were measured in the rat in vivo under anaesthesia by insertion into the descending colon of an agarose gel cylinder simulating the faeces. Functional studies were completed by histological analyses. In the first set of experiments, rats received 3.8 Gy with various neutron percentages and were studied from 1 to 14 days after exposure. In the second set of experiments, rats were exposed to increasing doses of irradiation (1-4Gy) with a high neutron percentage (87%n) and were studied at 4 days after exposure. RESULTS AND CONCLUSIONS: The absorptive capacity of rat colon was diminished by irradiation at 3-5 days, with a nadir at 4 days. The results demonstrate that an increase in the neutron proportion is associated with an amplification of the effects. Furthermore, a delay in the re-establishment of normal absorption was observed with the high neutron proportion (87%n). A dose-dependent reduction of water absorption by rat colon was also observed following neutron irradiation (87%n), with a 50% reduction at 3 Gy. Comparison of this dose-effect curve with the curve obtained following gamma (60)Co-irradiation indicates an RBE of 2.2 for absorptive colonic function in rat calculated at 4 days after exposure.

Absorption↗

PubMed2002

Potential role of the membrane in the development of intestinal cellular damage after whole-body gamma irradiation of the rat.

Our study emphasizes the effect of gamma irradiation on intestinal cell membrane fluidity and addresses the potential relationships existing between radiation-induced lipoperoxidation, membrane fluidity, and changes in membrane protein activities. Male Wistar rats were exposed to an 8-Gy total body irradiation (60Co source) and studied 1, 4, and 7 days after irradiation (D1, D4, and D7). Membrane enzyme activities and fluorescence anisotropy were determined on small intestinal crude membrane preparations. The supernatants of membrane preparations as well as plasma were used for malonedialdehyde (MDA) quantification. The effect of carbamylcholine on electrical parameters was estimated on distal ileum placed in Ussing chambers. We observed a decrease in fluorescence anisotropy for at least 7 days, an increase in membrane production of MDA at D4, a decrease in membrane enzyme activities at D4, but an amplification of carbamylcholine-induced increase in short-circuit current at D4 and D7. Furthermore, correlations were observed between the 1,6-diphenyl-1,3,5-hexatriene anisotropy coefficient and sucrase activity and between MDA levels and leucine aminopeptidase activity. Thus, total body irradiation induces changes in intestinal membrane fluidity and an increase in lipoperoxidation. These modifications may have an impact on the activity of membrane proteins involved in intestinal function.

Animals↗

PubMed2002

Alterations of the VIP-stimulated cAMP pathway in rat distal colon after abdominal irradiation.

Ionizing radiation induces hyporesponsiveness of rat colonic mucosa to vasoactive intestinal peptide (VIP). Possible mechanisms responsible for this hyporesponsiveness of the cAMP communication pathway in rat colon were investigated. VIP- and forskolin-stimulated short-circuit current (I(sc)) responses were studied after a 10-Gy abdominal irradiation in Ussing chambers as well as in single, isolated crypts. Adenylyl cyclase (AC) activity and VIP receptor characteristics were determined in mucosal membrane preparations. In addition, alterations in crypt morphology were studied. Impaired secretory responses to VIP and forskolin were observed 4 days after irradiation (decrease of 80%). cAMP analog-stimulated I(sc) responses were unchanged. In isolated crypts, VIP- and forskolin-stimulated cAMP accumulation was markedly reduced by 80 and 50%, respectively. VIP-stimulated AC activity and VIP receptor number were decreased in membrane preparations. No major change of cellularity was associated with these functional alterations. In conclusion, the decreased secretory responses to VIP of rat colon are associated with reduced cAMP accumulation, decreased AC activity, and diminution of VIP receptor numbers without a marked decrease of crypt cell number.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed2002

Characterization of altered absorptive and secretory functions in the rat colon after abdominal irradiation: comparison with the effects of total-body irradiation.

The aim of this work was to determine the alterations in the absorptive and secretory functions of the rat colon after abdominal irradiation and to compare the effects of abdominal and whole-body irradiation. Rats received an abdominal irradiation with 8 to 12 Gy and were studied at 1, 4 and 7 days after exposure. Water and electrolyte absorption was measured in vivo by insertion of an agarose cylinder into the colons of anesthetized rats. In vitro measurements of potential difference, short-circuit current and tissue conductance were performed in Ussing chambers under basal and agonist-stimulated conditions. Most of the changes appeared at 4 days after abdominal irradiation. At this time, a decrease in water and electrolyte absorption in the colon was observed for radiation doses > or = 9 Gy. The response to secretagogues (VIP, 5-HT and forskolin) was attenuated after 10 and 12 Gy. Epithelial integrity, estimated by potential difference and tissue conductance, was altered from 1 to 7 days after 12 Gy abdominal irradiation. These results show that the function of the colon was affected by abdominal irradiation. Comparison with earlier results for total-body irradiation demonstrated a difference of 2 Gy in the radiation dose needed to induce changes in the function of the colon.

Abdomen↗

PubMed2001

Intestinal and colonic motor alterations associated with irradiation-induced diarrhoea in rats.

Localized application of ionizing radiation to the gastrointestinal tract frequently elicits responses, which include diarrhoea. The origin of this symptom is not clear but has been attributed to loss of epithelial integrity, together with alterations in motility and increased secretion. The purpose of this study was to examine whether a 10 Gy abdominal gamma irradiation leads to an inflammatory reaction, and to compare intestinal and colonic motility in controls and abdominally irradiated rats 1, 3 and 7 days after irradiation, using an electromyographic technique. The motility parameters analysed were the frequency and velocity of propagation of migrating myoelectric complexes (MMC) in the jejunum and colonic spike activity (long spike bursts; LSB) per 10 min in fasted rats. The MMC frequency was significantly reduced on days 1 and 7 after irradiation and the MMC pattern was markedly disrupted on day 3. The frequency of colonic LSB was significantly reduced on days 1, 3 and 7. Mouth to anus transit was significantly accelerated on day 3 only and diarrhoea was observed at this time. Myeloperoxidase activity in the jejunum and colon was also increased on this day only. It is concluded that irradiation-induced diarrhoea occurs contemporaneously with disruption of MMC in the small intestine.

Animals↗

PubMed2001

Absence of protective role of afferent nerves in early intestinal mucosal alterations induced by abdominal irradiation in rats.

PURPOSE: To assess the early effects of primary afferent nerve suppression by systemic treatment with the neurotoxin capsaicin in an acute model of abdominal irradiation in rats (10Gy, gamma). MATERIALS AND METHODS: Changes in myeloperoxidase (MPO) activity, calcitonin gene-related peptide (CGRP) tissue content, number of mast cells and apoptotic cells were determined in jejunum and ileum in four groups of rat male Wistar (vehicle sham-irradiated, vehicle irradiated, capsaicin sham-irradiated and capsaicin irradiated) at 1 and 3 days post-irradiation. RESULTS: In vehicle irradiated rats, CGRP was significantly increased from the first day after irradiation in jejunal mucosa; MPO activity increased in both segments at day 3 but not at day 1 after irradiation; the number of detectable mucosal mast cells dropped to nearly zero on days 1 and 3, while the apoptotic cells in the intestinal mucosa were significantly increased at day 1. Similar results were obtained for mast cells and apoptosis in capsaicin irradiated rats as compared to capsaicin sham-irradiated rats, while MPO activity was significantly increased and CGRP concentration in jejunal mucosa significantly decreased from the first day in these rats in comparison with capsaicin sham-irradiated rats. CONCLUSIONS: Intestinal sensory innervation seems not to have a major protective role against a radiation-induced intestinal inflammatory reaction.

Animals↗

PubMed2001

The example of gastrointestinal damage induced by ionising radiation: are there accessible markers?

Ionising radiation exposure occurs during radiotherapy, diagnostic tests or by accident. In all cases the gastrointestinal tract, which is highly sensitive to radiation, may be at risk. Each region may respond differently to radiation exposure which to some extent is reflected by clinical symptoms. The evaluation of injury, whether acute or chronic, depends on the utilization of a variety of techniques. It appears that no definitive tests exist and that a multiparametric analysis should be undertaken. This review addresses the question of accessible markers associated with radiation-induced intestinal pathologies. Several approaches are discussed which include clinical observations, measurement of faecal parameters, changes in inflammatory mediators and possible applications of imaging techniques.

Animals↗

PubMed2000

Radiation induced cytochrome c release causes loss of rat colonic fluid absorption by damage to crypts and pericryptal myofibroblasts.

BACKGROUND: Therapeutic or accidental exposure to radiation commonly causes gastrointestinal disturbances, including diarrhoea. Rats subjected to whole body ionising radiation at a dose of 8 Gy lose their capacity to absorb fluid via the descending colon after four days. After seven days, fluid absorption recovers to control levels. AIMS: To investigate the effect of ionising radiation on colonic permeability together with its effect on mitochondria dependent apoptotic signals and intercellular adhesion molecules. METHODS: Rats were irradiated with doses of 0-12 Gy. Colonic permeability was measured by accumulation of fluorescein isothiocyanate (FITC) dextran in crypt lumens. Changes in levels of cytochrome c, caspase 3, E and OB cadherin, beta-catenin smooth muscle actin, and collagen IV were assessed using immunocytochemistry with confocal microscopy. RESULTS: Cytosolic cytochrome c increased after 8 Gy (t(1/2) 1.4 (0.6) hours) and peaked at approximately six hours. Caspase 3 increased more slowly, particularly in crypt epithelial cells (t(1/2) 57 (14.5) hours). Pericryptal myofibroblasts disintegrated within 24 hours as was evident from loss of OB cadherin and smooth muscle actin. This coincided with increased crypt permeability to dextran. Intercellular adhesion between crypt luminal cells was not lost until day 4 when both beta-catenin and E-cadherin were minimal. The half maximal dose-response for these effects was in the range 2-4 Gy. Recovery of colonic transport was concurrent with recovery of pericryptal smooth muscle actin and OB cadherin. The pan caspase inhibitor Z-Val-Ala-Asp.fluoromethylketone (1 mg/kg per day) had a small effect in conserving the pericryptal sheath myofibroblasts and sheath permeability but had no systemic therapeutic effects. CONCLUSIONS: These data suggest that radiation damage to the colon may be initiated by mitochondrial events. Loss of crypt fluid absorption and increased permeability coincided with decreased intercellular adhesion between crypt epithelial cells and loss of pericryptal sheath barrier function.

Animals↗

PubMed2000

Changes in 5-HT-mediated pathways in radiation-induced attenuation and recovery of ion transport in rat colon.

Whole body exposure to high doses of ionizing radiation is associated with small intestinal and colonic dysfunction, the etiology of which remains unknown. In this study, we investigated the role of both neural and nonneural 5-hydroxytryptamine (5-HT)-mediated pathways in radiation-induced attenuation and recovery of colonic secretory function. Rats were exposed to whole body 10-Gy gamma irradiation, and distal colonic tissues were studied in Ussing chambers 1, 3, and 7 days after exposure. Tissue responses to exogenously added 5-HT (nonneural pathway) and electrical field stimulation (EFS; neural pathway) were performed, and 5-HT receptor subtypes implicated in both responses were determined using three different 5-HT receptor antagonists: methysergide (5-HT(2/1C)), granisetron (5-HT(3)), and SDZ-205,557 (5-HT(4)). Maximal responses to exogenously added 5-HT were decreased at 1 and 3 days and returned to control values at 7 days. Responses to exogenous 5-HT were insensitive to both 5-HT(2/1C) and 5-HT(3) antagonists and to TTX but were totally inhibited by SDZ-205, 557 in both control and irradiated tissues. Responses to EFS were decreased 1 and 3 days after exposure and returned to control values at 7 days. In control tissues and 1 and 3 days after exposure, EFS responses were insensitive to both 5-HT(2/1C) and 5-HT(4) antagonists but reduced by granisetron in control (51%) and at 1 (64%) and 3 days (58%) after exposure. Granisetron was more effective at 7 days (73% inhibition), which was concomitant with the appearance of a 5-HT(4) antagonist-sensitive pathway (40% inhibition). In conclusion, neural and nonneural 5-HT-mediated pathways involve 5-HT(3) and 5-HT(4) receptors, respectively, in control as well as in irradiated tissues 1 and 3 days after exposure. Conversely, the recovery of colonic transport is associated with additional 5-HT(3)-mediated pathways, probably in combination with 5-HT(4) receptors.

Animals↗