Biomedical subjects

M J Fargeas

Publications and source records attributed to M J Fargeas.

At least 19 recordsLinked to original sources

PubMed1996

Decrease in sensitisation rate and intestinal anaphylactic response after nitric oxide synthase inhibition in a food hypersensitivity model.

BACKGROUND: Although nitric oxide (NO) has been found to have a role in gut inflammation and to modulate immunoglobulin production, little is known about its part in food hypersensitivities. AIM: This study aimed to evaluate the role of NO through the inhibition of constitutive and inducible NO synthase (cNOS and iNOS respectively) on the sensitisation process (antibody titres) and on intestinal anaphylactic responses (colonic hypersecretion upon antigen challenge). ANIMALS AND METHODS: Guinea pigs sensitised to cow's milk proteins were treated either during the sensitisation period or before antigen challenge by N-nitro-L-arginine methyl ester (L-NAME) (inhibiting both cNOS and iNOS) or amino-guanidine (selective iNOS inhibitor). RESULTS: Chronic treatment by L-NAME or aminoguanidine reduced antibody titres and the secretory response to antigen challenge. In contrast, only L-NAME administered before challenge was able to antagonise the hypersecretion induced by the challenge. CONCLUSIONS: NO generated by iNOS has a role in the sensitisation process: iNOS inhibition results in lower rates of antibodies leading to a reduced secretory response upon challenge. In contrast, blockade of colonic hypersecretion by L-NAME but not by aminoguanidine suggests that NO via cNOS is a key mediator in intestinal anaphylactic reactions.

Animals↗

PubMed1995

c-fos expression in specific rat brain nuclei after intestinal anaphylaxis: involvement of 5-HT3 receptors and vagal afferent fibers.

The c-fos immediate-early gene is acutely induced in brain after various stimuli from the digestive tract. 5-HT3 receptors and vagal afferents have been found involved in intestinal motor disturbances induced by intestinal anaphylaxis. Our aim was to determine whether intestinal anaphylaxis activates brain structures, using c-fos expression, and to evaluate the modulation of c-fos induction by 5-HT3 receptors and vagal afferents. The effects of antigen challenge on intestinal motility were evaluated in ovalbumin-sensitized Hooded Lister rats chronically fitted with NiCr electrodes in the jejunal wall. Intestinal motility was assessed in conscious rats pretreated or not by perivagal capsaicin or a 5-HT3 antagonist (ondansetron). In sensitized rats, ovalbumin disrupted for 62.4 +/- 9.5 min the jejunal migrating motor complexes (MMC) and an important c-fos expression was detected in the nucleus tractus solitarius (NTS), lateral parabrachial nucleus (LPB) and paraventricular nucleus of the hypothalamus (PVN). Intraperitoneal administration of ondansetron or perivagal capsaicin treatment significantly reduced the duration of MMC disruption and attenuated markedly c-fos staining in the 3 brain sites. In contrast, intracerebroventricular administration of ondansetron significantly reduced jejunal motor alterations but did not diminish the c-fos expression, suggesting a role of central 5-HT3 receptors in the efferent control of the intestinal disturbances. Blockade of both c-fos expression and MMC disruption by systemic ondansetron and by perivagal capsaicin indicates that some brainstem nuclei are involved in digestive disturbances after intestinal anaphylaxis, and reflects an involvement of peripheral 5-HT3 receptors on vagal afferents. The reduction of c-fos staining in NTS as well as in LPB and PVN after perivagal capsaicin suggests that the NTS is the primary relay in the activation of the central nervous system during intestinal allergic challenge.

Afferent Pathways↗

PubMed1995

Boosted systemic immune and local responsiveness after intestinal inflammation in orally sensitized guinea pigs.

BACKGROUND & AIMS: Intestinal inflammation resulting in disruption of the mucosal barrier function has been proposed as a cause of increased incidence of allergic diseases. This study was designed to evaluate whether intestinal inflammation is able to change the immune responsiveness to sensitization and antigen challenge responses. METHODS: Guinea pigs orally sensitized to cow's milk proteins were either treated or not treated with trinitrobenzenesulfonic acid (TNBS) to induce intestinal inflammation and compared with control animals (not sensitized). Systemic immune and local responsiveness to antigen challenge were assessed by measuring antibody serum titers, colonic fluid secretion, mucosal histamine level, and mucus depletion. Intestinal permeability was evaluated from 51Cr-ethylenediaminetetraacetic acid (EDTA) recovery and beta-lactoglobulin serum level. RESULTS: Immunoglobulin E titers were higher in TNBS-treated animals than in non-TNBS-treated sensitized animals. Antigen challenge in TNBS-treated animals induced a fourfold increase of colonic secretion and greater histamine and mucus depletion than in non-TNBS-treated animals. Permeability to 51Cr-EDTA increased 5 days after TNBS treatment but was unchanged after antigen challenge. In contrast to controls, beta-lactoglobulin was not detected in the sera of challenged sensitized and TNBS-treated animals. CONCLUSIONS: Intestinal inflammation increasing gut permeability enhances the sensitization process. Therefore, local anaphylactic reactions are exacerbated after antigen challenge.

Analysis of Variance↗

PubMed1994

Role of 5-HT3 receptors and afferent fibers in the effects of mast cell degranulation on colonic motility in rats.

BACKGROUND/AIMS: Mediators released by mast cell degranulation contribute to digestive motility disturbances. According to the role of serotonin and the close proximity of mast cells to nerves, the aim of this study was to assess the role of 5-hydroxytryptamine 3 (5-HT3) receptors, capsaicin-sensitive afferent fibers, and some of their neuropeptides (substance P and calcitonin gene-related peptide) in colonic motor alterations induced by degranulation of mast cells by the compound BrX-537A. METHODS: The effects of BrX-537A (2 mg/kg intraperitoneally) were determined by electromyography in conscious rats implanted with electrodes in the cecocolonic wall. RESULTS: BrX-537A inhibited cecocolonic myoelectric activity for 7-8 hours. A primary and dramatic reduction of spike burst frequency, lasting 30 minutes, was affected by none of the pretreatments tested. The following inhibition was fully antagonized by ketotifen (mast cell stabilizer), granisetron and ondansetron (5-HT3 antagonists), RP-67,580 (NK1 antagonist), and perivagal capsaicin pretreatment. A temporary blockade was observed after administration of CP-96,345 (NK1 antagonist) and in rats systemically treated by capsaicin. The calcitonin gene-related peptide antagonist hCGRP(8-37) did not modify the BrX-537A-induced inhibition. CONCLUSIONS: 5-HT3 receptors, sensory afferent fibers reaching the vagus nerves, and substance P are major components of the colonic motor inhibition induced by mast cell degranulation.

Afferent Pathways↗

PubMed1994

Induction of postprandial intestinal motility and release of cholecystokinin by polyamines in rats.

Polyamines are known to play a major role in postprandial adaptation of the digestive tract. Experiments were designed to determine whether ingested polyamines induce change in intestinal motility associated with a cholecystokinin (CCK) release and whether endogenous polyamines are involved in the intestinal and colonic motor response to a meal. Intestinal and colonic motility was assessed in rats equipped with intestinal electrodes, and plasma CCK was determined using a bioassay. Orogastric administration of putrescine, spermidine, or spermine (20 mumol) disrupted intestinal migrating myoelectric complexes (MMCs) and increased the frequency of colonic spike bursts. After a 6-day treatment with the ornithine decarboxylase inhibitor alpha-difluoromethylornithine, the duration of postprandial disruption of MMCs, but not the stimulation of colonic motility, induced by a 3-g meal was significantly reduced. The duration of MMC disruption and the increase in colonic spike burst frequency after spermidine administration (20 mumol) were significantly reduced by CCK-A and CCK-B antagonists. Eight minutes after saline administration plasma CCK concentration was 0.9 +/- 0.4 pM; it rose to 4.7 +/- 2.8 pM, 8 min after spermidine (20 mumol). These results indicate that exogenous polyamines disrupt intestinal MMCs and stimulate colonic motility through a release of CCK acting at CCK-A and CCK-B receptors and suggest that endogenous polyamines are involved in the postprandial control of intestinal motility.

Animals↗

PubMed1993

Clonazepam-induced intestinal motor disturbances are linked to central nervous system release of cholecystokinin in rats.

The central and peripheral effects of clonazepam (central benzodiazepine receptor agonist) on intestinal myoelectrical activity and the origin of the effects were evaluated in conscious rats, chronically fitted with Nichrome electrodes implanted on the jejunum and with an intracerebroventricular (i.c.v.) cannula. Administered intraperitoneally (i.p.) in 12-h fasted rats, clonazepam (0.05 to 0.5 mg/kg) dose dependently disrupted jejunal cyclic migrating myoelectric complexes, characterizing the fasted state, which were replaced by a permanent irregular spiking activity, lasting 259 +/- 37 min for clonazepam at the dose of 0.5 mg/kg. This disruption of migrating myoelectric complexes occurred after a delay which increased with increasing clonazepam doses. In contrast, injected i.c.v. at doses from 1 microgram/kg to 1 mg/kg, clonazepam did not alter the migrating myoelectric complexes pattern of the small intestine. Injected i.p., flumazenil (central benzodiazepine receptor antagonist) (1 mg/kg) but not PK 11-195 (peripheral benzodiazepine receptor antagonist) (5 mg/kg) suppressed the effects of i.p. clonazepam (0.1 mg/kg). Administered i.c.v., 10 min prior to clonazepam (0.1 mg/kg i.p.), devazepide (CCKA receptor antagonist) at a dose as low as 10 ng/kg reduced the migrating myoelectric complex disruption induced by clonazepam. L365-260 (CCKB receptor antagonist) administered i.c.v reduced the migrating myoelectric complex disruption at 10-fold higher doses and loxiglumide (CCKA receptor antagonist) injected i.c.v, at 100-fold higher doses. When administered i.p. neither devazepide nor L365-260 affected the duration of migrating myoelectric complex disruption induced by clonazepam (0.1 mg/kg i.p.) or its delay of occurrence at doses lower than 0.1 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Central action of interleukin 1 beta on intestinal motility in rats: mediation by two mechanisms.

BACKGROUND: Interleukin 1 (IL-1) can influence gut functions by inhibiting gastric acid secretion. This study was performed to investigate the effects of IL-1 on intestinal motility and the mechanisms involved. METHODS: The effects of IL-1 beta were determined by electromyography in conscious rats with implanted electrodes and a permanent catheter in a lateral brain ventricle. RESULTS: Intracerebroventricular IL-1 beta (15 ng) administered to fed rats immediately stimulated cecocolonic spike bursts and caused a migrating myoelectric complex pattern after a delay in the small intestine. Tenfold higher doses of peripherally administered IL-1 beta did not promote similar reactions. The IL-1 antagonist reduced the small intestinal effect of IL-1 beta and blocked the cecocolonic stimulation. Indomethacin and SC 19220 reduced the small intestinal effects but did not antagonize the increase in cecocolonic contractions. In contrast, alpha-helical CRF9-41 blocked the increase of cecocolonic contractions but did not antagonize the IL-1 beta-induced effects on the small intestine. CONCLUSION: IL-1 beta's effects on intestinal motility can be mainly ascribed to a central action. The cecocolonic stimulation may be mediated by brain corticotropin-releasing factor, whereas the small intestinal effects involve a prostaglandin mediation.

Animals↗

PubMed1993

Involvement of capsaicin-sensitive afferent nerves in the intestinal motor alterations induced by intestinal anaphylaxis in rats.

Alteration of intestinal myoelectrical activity is a characteristic feature of food protein-induced intestinal anaphylaxis in the conscious rat. The motility changes induced by antigen challenge were appraised in egg-albumin-sensitized rats, chronically implanted with NiCr electrodes in the duodenojejunal wall. Intraduodenal infusion of egg albumin given to fasted sensitized rats triggered a disruption of the cyclic pattern of small intestinal motility lasting 79.1 +/- 23.3 min. The duration of the challenge effect on intestinal myoelectrical activity was significantly reduced by systemic capsaicin pretreatment (125 mg/kg) but to a lesser extent by perivagal capsaicin. Substance P (SP) antagonists (SP 4-11 and CP 96.345) and atropine were also able to shorten the duration of the antigen-challenge-induced alteration of intestinal motility. It is concluded that SP and capsaicin-sensitive afferent nerve endings play an important role in the intestinal anaphylaxis-induced disturbances of intestinal motility.

Afferent Pathways↗

PubMed1993

[Role of serotonin and histamine in the effects of degranulation of mast cells on the colonic motility and the transit. Experimental study in rats].

The aim of this work was to describe the alterations of colonic motility and transit induced by an experimental, histologically verified, degranulation of mast cells, provoked by the compound BrX-537A, and to determine the role of serotonin and histamine by specific antagonists, in the rat. Colonic myoelectrical activity was inhibited by BrX-537A (2 mg/kg IP) in a biphasic manner. The initial profound inhibition, lasting 30 min, during which the frequency of spike bursts decreased from 9.2 +/- 1.1 to 1.4 +/- 0.5/10 min, was followed by a sustained (5 h) period of moderate inhibition (5.2 +/- 0.5 spike bursts/10 min). In the same way, BrX-537A increased the mean retention time of a marker injected in the proximal colon (10.8 +/- 1.4 h vs 7.4 +/- 0.4 h). Neither serotoninergic nor histaminergic antagonists, at a dose of 1 mg/kg IP, modified the primary drastic inhibition of colonic motility during the first 20 minutes. After, a selective time-related blockade of this inhibition was observed. Granisetron blocked the inhibition from the 30th minute on, methysergide from the 120th minute on, and chlorpheniramine, between the 20th and 60th minutes. In conclusion, the inhibitory effect of mast cell degranulation depends on serotonin and histamine release, in a time-related manner, and implicates the H1, 5-HT3 and 5-HT1 or 2 receptors.

Animals↗

PubMed1992

Relationship between mast cell degranulation and jejunal myoelectric alterations in intestinal anaphylaxis in rats.

The effects of two degranulators of mast cells and intestinal anaphylaxis on jejunal myoelectric activity were compared in rats fasted for 15 hours. Attempts to antagonize the motility changes were performed using antagonists of histamine and serotonin and a cyclooxygenase and lipoxygenase inhibitor. Hooded Lister rats were chronically fitted with electrodes implanted in the jejunal wall. A group of rats was sensitized to egg albumin and challenged 14 days later by intraduodenal infusion of antigen. Sensitized animals had serum titers greater than or equal to 1:64. The other group was administered with mast cells degranulators. Both 48/80 (1 mg/kg), a degranulator of connective mast cells, and bromolasalocid (2 mg/kg), acting on connective and mucosal mast cells, induced a phase of total spiking inhibition followed by a progressive irregular spiking activity until the recovery of migrating myoelectric complex pattern (about 3 hours after injection). In contrast, antigen challenge disrupted the migrating myoelectric complex pattern, which was replaced by a peculiar pattern characterized by propagated spike burst, lasting 98 +/- 11.3 minutes. Chlorpheniramine (1 mg/kg) antagonized only the inhibitory phase induced by degranulators and was ineffective on the intestinal anaphylaxis-induced motor changes. Methysergide (1 mg/kg) and indomethacin (5 mg/kg) significantly reduced the degranulator effects as well as the anaphylaxis-induced alterations of intestinal motility. It is concluded that anaphylaxis-induced motor disturbances are relevant to mucosal mast cell degranulation involving 5-hydroxytryptamine and arachidonic acid derivative products, whereas histamine release appears to be a minor component.

Anaphylaxis↗

PubMed1992

Physical dependence on diazepam: precipitation of abstinence syndromes by peripheral and central benzodiazepine receptor antagonists.

This work was performed to compare withdrawal symptoms induced by the administration of the central vs. peripheral benzodiazepine antagonists in rats treated chronically with diazepam (15 mg/kg, SC) for 8 days. Withdrawal was expressed as motor, autonomic, and behavioral signs. Significant withdrawal occurred after the administration of both flumazenil (15 and 20 mg/kg, IP) and PK11195 (5 and 10 mg/kg, IP). With these doses, PK11195 induced diarrhea and decreased motor activity more than did flumazenil. These preliminary results suggest that peripheral benzodiazepine receptors are involved in the withdrawal syndrome in diazepam-dependent rats.

Animals↗

PubMed1992

Gastrointestinal motor alterations induced by precipitated benzodiazepine withdrawal in rats.

The effects of benzodiazepine withdrawal on intestinal motor activity and propulsion were investigated in two groups of diazepam-dependent rats (15 mg/kg/day for 8 days). Withdrawal was precipitated by injection of two benzodiazepine antagonists (Ro 15.1788 and PK 11.95) acting on central and peripheral-type receptors, respectively. Intestinal motor activity was assessed by implanting electrodes for long-term electromyographic recordings. Gastrointestinal transit was evaluated after gavage by a marker (51CrO4Na2) and radioactivity counting. Both RO 15.1788 (15 mg/kg) and PK 11.195 (5 mg/kg) triggered an abstinence syndrome with behavioral and autonomic signs. At the intestinal level, Ro 15.1788 induced a phase of strong irregular spiking activity (173 +/- 63 min) which remained located in the duodenum. In contrast, PK 11.195 induced a period of propagated myoelectric complexes characterized by phases II and III of high amplitude. The cecal frequency was doubled during the 1st hr after withdrawal induced by the two antagonists. Both Ro 15.1788 and PK 11.195 at this dosage had no effect per se on intestinal motility in vehicle-treated rats. In the second group of rats, gastric emptying was enhanced by 49.4 and 45.6% by Ro 15.1788 and PK 11.195, respectively. In contrast, PK 11.195 was able to accelerate the intestinal transit more than did Ro 15.1788 (geometric center, 5.9 +/- 0.43 and 5.3 +/- 0.49, respectively, vs. 4.1 +/- 0.31 in control rats). Our study shows that precipitated benzodiazepine withdrawal in diazepam-dependent rats induces alterations of the intestinal myoelectrical activity leading to an increase of the gastrointestinal transit. Central and peripheral-type receptors are involved in these effects.

Animals↗

PubMed1991

Involvement of 5-hydroxytryptamine in the intestinal motor disturbances induced by mast cell degranulation in rats.

Fasted rats with chronically implanted electrodes were used for investigation of the effects of mast cell degranulation induced by compound 48/80 and BrX-537A and their antagonism by previous administration of 5-hydroxytryptamine (5-HT) antagonists on duodenal and jejunal myoelectric activity. Administered i.p., both 48/80 (1 mg/kg i.p.) and BrX-537A (2 mg/kg i.p.) abolished the intestinal spiking activity of duodeno-jejunum with a progressive recovery, BrX-537A being less active. These effects were dose-related. Injected prior to 48/80, methysergide (1 mg/kg) reduced by about 80% both duodenal and jejunal inhibition of spiking activity with early recovery of a normal pattern. In contrast, ketanserin (1 mg/kg) had selective reducing effects on the duration of the spiking inhibition induced by 48/80 and BrX-537A on the duodenum only. Zacopride (1 mg/kg) and ICS 205-930 (50 micrograms/kg) shortened and suppressed, respectively, the inhibition of intestinal spiking activity with early restoration of intestinal motility in both duodenum and jejunum. We conclude that, in fasted rats (i) the degranulation of peritoneal mast cells induces alterations in intestinal myoelectric activity through the release of 5-HT (ii) these effects are mainly mediated through both 5-HT1 and 5-HT3 receptors.

Animals↗

PubMed1989

Involvement of different receptors in the central and peripheral effects of histamine on intestinal motility in the rat.

The effects of histamine on intestinal motility have been investigated in conscious rats, fed or fasted, using an electromyographic method. Histamine peripherally administered (10 mg kg-1) in 15 h fasted rats induced an inhibition followed by a period of irregular spiking activity disrupting the duodenojejunal migrating myoelectric complexes (MMC) and suppressed the postprandial motor spiking activity when administered 50 min after a meal. The selective agonist of the H1-receptors, 2-pyridylethylamine (2-PEA) induced an irregular spiking activity while dimaprit acting on H2-receptors, inhibited the MMC pattern. Effects of peripherally administered histamine were antagonized by previous administration of chlorpheniramine (0.5 mg kg-1 i.p.) and in a lesser extent by cimetidine (10 mg kg-1 i.p.). Histamine (1-10 micrograms) administered intracerebroventricularly (i.c.v.) in fasted rats increased the motor cycle frequency and immediately restored the MMC pattern when given to fed rats. Among the three agonists of the H1- H2- and H3-receptors (2-PEA, dimaprit and R-alpha-methylhistamine, respectively) only R-alpha-methylhistamine (1-10 micrograms i.c.v.) was able to reproduce this effect. It is concluded that the effects of histamine on intestinal motility were centrally and peripherally mediated involving mainly H1-receptors at the peripheral level and H3-receptors at the CNS level.

Animals↗

PubMed1989

Involvement of different mechanisms in the stimulatory effects of cholecystokinin octapeptide on gastrointestinal and colonic motility in dogs.

The effects of an intravenous infusion of cholecystokinin octapeptide (CCK-8, 1 microgram.kg-1.h-1) were investigated in conscious fasted dogs chronically fitted with strain-gauge transducers on the antrum, the jejunum, and the colon. Attempts to antagonize the increase of motility appearing at the three levels during CCK infusion were made using different blockers to elucidate the mechanisms involved. Asperlicin (a specific CCK antagonist) blocked the effects of CCK-8 at the three levels, while atropine and somatostatin were only effective in the jejunum and colon. Methyl-levallorphan (a mu-opiate antagonist that poorly crosses the blood-brain barrier) antagonized the CCK-induced colonic stimulation when intracerebroventricularly administered. Serotonin, histamine, substance P, and K-antagonists as well as a benzodiazepine did not modify the CCK-8 induced stimulation. It was concluded that the stimulatory effect of CCK-8 resulted from (a) a direct stimulation of the smooth muscle cells at gastric level, (b) a cholinergic activation of the jejunum and the colon, and (c) the involvement of a mu-opioid central component in the colonic response only.

Animals↗

PubMed1989

Vagally mediated inhibition of acoustic stress-induced cortisol release by orally administered kappa-opioid substances in dogs.

The effects of oral vs. iv administration of kappa- and mu-opioid agonists on plasma cortisol release induced by acoustic stress (AS) were evaluated in fasted dogs with an implanted jugular catheter. AS was induced by 1 h of music (less than or equal to 86 decibels) played through earphones and was accompanied by a 382% maximal rise in plasma cortisol after 15-30 min. Administered orally 30 min before the AS session, both U-50488 (0.1 mg/kg) and PD 117-302 (0.05 mg/kg) significantly (P less than or equal to 0.01) decreased (by 71.2% and 80.9%, respectively) the maximal increase in plasma cortisol induced by AS, while bremazocine, morphine, as well as iv administration of U-50488 at similar doses were ineffective. The effects of U-50488 and PD 117-302 orally administered (0.1 mg/kg) on the hypercortisolemia induced by AS were abolished by pretreatment with iv naloxone (0.1 mg/kg) or MR 2266 (0.1 mg/kg). Naloxone given alone significantly (P less than 0.01) increased basal plasma cortisol, without affecting cortisol increase induced by AS. Vagotomy abolished the effects of orally administered U-50488 on the AS-induced increase in plasma cortisol. Neither U-50488 nor PD 117302 (0.1 mg/kg, orally) reduced the increase in plasma cortisol induced by intracerebroventricular administration of ovine CRF (100 ng/kg). It is concluded that kappa- but not mu-opioid agonists are able to inhibit the stimulation of the hypothalamo-pituitary-adrenocortical axis induced by AS by acting selectively on peripheral kappa-receptors located in the wall of the proximal gut. This action is neurally mediated through afferent vagal fibers affecting central nervous system release of CRF induced by a centrally acting stressor.

Administration, Oral↗

PubMed1988

Involvement of central noradrenergic pathways in the control of intestinal motility in rats.

Small intestinal motility was monitored in conscious rats chronically fitted with intraparietal electrodes, the third and fourth weeks after intraperitoneal administration of saline (controls) or N-(2-chloro-ethyl)-N-ethyl-2-bromobenzylamine (DSP-4, 50 mg/kg), a noradrenergic neurotoxin. Norepinephrine concentrations determined 35 days later in the forebrain and the brainstem were dramatically reduced in DSP-4-treated rats. The frequency of intestinal cycles of motor activity observed after 15 h of fast was very irregular and significantly lower in DSP-4-treated rats. The disruption of the cyclic activity induced by feeding was uncomplete on the duodenum and significantly shorter on the jejunum after DSP-4 treatment. These data indicate that the central noradrenergic innervation plays an important role in the control of the small intestinal cyclic activity and its postprandial disruption.

Adrenergic Fibers↗

PubMed1988

Central and peripheral action of GABAA and GABAB agonists on small intestine motility in rats.

gamma-Aminobutyric acid (GABA) is known as a neurotransmitter in the central nervous system and in the enteric nervous system. The effects and the sites of action of GABA and of its GABAA (muscimol) and GABAB (baclofen) agonists were determined on intestinal motility of unanesthetized rats chronically fitted with intraparietal electrodes in the duodeno-jejunum and fasted for 8 h. GABA (6 mg/kg i.p.) induced a biphasic response i.e. a primary inhibition followed by a period of irregular spiking activity. Muscimol (4 mg/kg i.p.) inhibited the cyclic motor profile while baclofen (4 mg/kg i.p.) had a stimulatory effect chiefly at the duodenal level. Only baclofen intracerebroventricularly administered (1 microgram i.c.v.) was able to reproduce the intestinal motor effects observed after systemic injections. Bicuculline (a specific GABAA antagonist) blocked the inhibition induced by GABA and muscimol; atropine (i.p. and i.c.v.) antagonized the irregular spiking activity induced by GABA and baclofen. It is concluded that the dual effect of GABA can be explained by an action at 2 subtypes of receptors: GABAA and GABAB. Stimulation of GABAA receptors induced peripherally mediated inhibition of the duodeno-jejunal motility. On the contrary stimulation of the GABAB receptors increased and disrupted duodenal cyclic motility by a central action involving central and peripheral muscarinic receptors.

Animals↗