Biomedical subjects

J Fioramonti

Publications and source records attributed to J Fioramonti.

At least 145 records · Page 8Linked to original sources

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↗

PubMed1988

Opposite effects of kappa-opioid agonists on gastric emptying of liquids and solids in dogs.

The influence of oral (p.o.) administration of kappa-(U-50488, tifluadom) and mu- (morphine, DAGO) opioid substances on gastric emptying of liquids and solids in a standard canned dog food meal was evaluated using a double-radiolabeled technique in dogs fitted with gastric cannulas. One hour after feeding, 28.6% +/- 3.6% (mean +/- SD) of the solid phase and 27.1% +/- 8.6% of the liquid phase of the meal had been emptied. Both U-50488 and tifluadom given orally (0.01-0.1 mg/kg) significantly increased (p less than 0.05) the 1-h emptying of the solid phase of the meal by 23.1%-49.6%. In contrast, both drugs significantly reduced emptying of liquids. These effects were not reproduced when similar doses were given intravenously. Oral administration of morphine or DAGO (0.01-0.1 mg/kg) did not affect gastric emptying, whereas an inhibited emptying of solids was observed for morphine at a higher dose (1 mg/kg p.o.). At a dose of 100 micrograms/kg i.v. both naloxone and MR 2266 (0.1 mg/kg) abolished the effects of orally administered U-50488 on gastric emptying of solids and liquids. It is concluded that kappa- but not mu-agonists act locally to alter gastric emptying of a standard meal in dogs, having opposite effects on solid and liquid phases. A selective local stimulation of kappa mucosal or submucosal receptors of the gastroduodenal area may explain such effects.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1988

Action of opiates on gastrointestinal function.

Opioid peptides and opioid receptors are distributed along the gastrointestinal (GI) tract, indicating endogenous opiates released peripherally may modulate GI motor and secretory functions. Animal studies have revealed that the effects of opiates on gut motility depend on the nature of the subclasses of receptor involved, the species and the part of bowel. Most opiates that have a selective or predominant mu agonist activity inhibit gastric motility and delay gastric emptying by acting centrally; delta and kappa agonist are inactive when injected systemically. The effect of opiates in delaying intestinal transit observed in man, rat and other species is related to an inhibition (rat) or a stimulation (dog and man) of intestinal contractions as premature phase III-like sequences. The constipating effects of morphine probably result mainly from its action on colonic motility. Morphine stimulates colonic motility in humans by action on both central and peripheral sites. This increase in colonic motility and the delay in colonic transit is associated with a reinforcement of tonic contractions and reduced propulsive waves. Opioid peptides have been shown to participate in the colonic motor response to eating in man and animals. Both delta and mu receptors are involved in the stimulatory effects of opiates on colonic motility, while kappa receptors inhibit colonic contractions, mainly by acting centrally. The effects of opiates on gastric acid secretion are still controversial but it has been well demonstrated that opiates act centrally to reduce pancreatic secretion in rats. Opiates also inhibit intestinal secretions via an action on the enteric nervous system as well as in the CNS. All these results reinforce the hypothesis that opioid peptides have a major physiological role in the control of gut motility and secretions, and these actions explain most of the pharmacological effects of opiate substances on the digestive tract.

Animals↗

PubMed1988

Inhibition of the colonic motor response to eating by pinaverium bromide in irritable bowel syndrome patients.

The effect of pinaverium bromide on the colonic motor response to eating was investigated in 10 irritable bowel syndrome patients, by means of an intraluminal probe supporting 8 groups of electrodes. At each site examined from transverse to sigmoid colon, the electromyograms exhibited 2 kinds of spike bursts: short spike bursts (SSB) localized at one electrode, and long spike bursts (LSB), isolated, propagated orally or aborally over a few centimeters, or aborally propagated over the whole length of the colon investigated (migrating long spike bursts, MLSB). Recordings were continuously performed over 24 hr. Each patient received at 7.00 p.m. on day 1 and at noon on day 2 an 800-1000 Kcal meal preceded by IV administration of pinaverium bromide (4 mg) or placebo. After placebo administration, the duration of LSB activity and the number of MLSB were significantly increased over 3 postprandial hr by comparison with the 2 hr preceding the meal. After pinaverium injection no significant postprandial change in LSB and MLSB activity was noted. The SSB activity was not modified after the meals preceded by placebo or pinaverium injection. These results suggest that the inhibitory action of pinaverium bromide on postprandial colonic motility may support the clinical efficacy of this agent in the treatment of the irritable bowel syndrome.

Adult↗

PubMed1988

Orally administered kappa but not mu opiate agonists enhance gastric emptying of a solid canned food meal in dogs.

The effects of oral administration of selective mu (D-Ala2, N-Me-p-nitro-Phe4, Gly5-ol-DAGO, morphine) and/or kappa (3,4 dichloro-N-methyl N [2-(1. fyrrolidinyl) cyclohexyl]-benzene acetamide-U-50488, tifluadom) or mixed agonist (N-desmethyltrimebutine) opioid on gastric emptying have been evaluated using a radiolabelled [57Co] canned food meal in dogs fitted with gastric cannulas. In control conditions (placebo) the percentage of solids emptied 1 h after feeding was 27.3 +/- 4.1%. When given orally at doses of 0.01 to 0.5 mg kg-1, U-50488 increased significantly (P less than 0.05) by 29.1 to 60.8% in a dose-related manner (r-0.94, P less than 0.01) the amount of gastric emptying of the meal in 1 h. This effect was reproduced by oral administration of tifluadom (0.01 to 0.1 mg kg-1) and by N-desmethyltrimebutine (0.1 to 1 mg kg-1). In contrast, the gastric emptying was unaffected by DAGO and morphine at low doses (0.01 and 0.1 mg kg-1) but significantly (P less than 0.05) slowed with higher doses of morphine. The increases in amount of gastric emptying induced by tifluadom, U-50488 and N-desmethyltrimebutine were abolished by previous administration of naloxone (0.1 mg kg-1 i.v.) and [(3-furylmethyl) noretazocine]-MR 22-66 (0.1 mg kg-1 i.v.). These results indicate that orally administered kappa, but not mu agonists at doses not exceeding 1 mg kg-1 enhance the amount of gastric emptying of a solid meal in dogs and suggest that this is due to a selective local stimulation of kappa mucosal or submucosal opiate receptors at antroduodenal level.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1988

Changes in colonic motility induced by sennosides in dogs: evidence of a prostaglandin mediation.

The effects of sennosides on colonic motility were investigated in eight conscious dogs chronically fitted with two strain gauge transducers in the proximal colon, an intracolonic silicone catheter and a polyethylene catheter implanted in a branch of the right colonic artery. Oral sennosides (30 mg/kg) inhibited colonic motility for 12 to 18 h after a three to six hours delay, and associated with giant contractions and diarrhoea. The minimal oral dose of sennosides to produce such changes varied from 5 to 15 mg/kg. Intracolonic sennosides at the minimal effective dose and at 30 mg/kg reproduced the effects of oral sennosides, but with a shorter latency (0.5-1.5 h). Intracolonic PGE2 (100 micrograms/kg) in viscous gel medium or intra-arterial PGE2 (10 micrograms/h) inhibited colonic motility and induced giant contractions often associated with defecation. The colonic motor changes induced by intracolonic sennosides at the minimal effective dose, but not those induced by intracolonic PGE2, were blocked by intra-arterial indomethacin (10 micrograms/h) or piroxicam (5 micrograms/h). These results suggest that colonic motor actions of sennosides are mediated through a local prostaglandins synthesis, as they were blocked by cyclooxygenase inhibitor and reproduced by PGE2.

Animals↗

PubMed1988

Involvement of endogenous opiates in regulation of gastric emptying of fat test meals in mice.

The role of endogenous opioids and cholecystokinin (CCK) in gastric emptying was investigated in mice killed 30 min after gavage with 51Cr-radiolabeled liquid meals. The meals consisted of 0.5 ml of milk or one of five synthetic meals containing arabic gum, glucose and/or arachis oil and/or casein. Naloxone (0.1 mg/kg sc) significantly (P less than 0.01) accelerated gastric emptying of milk and meals containing fat but did not modify gastric emptying of nonfat meals. The CCK antagonist asperlicin (0.1 mg/kg ip) increased by 25% gastric emptying of milk. The gastric emptying of meals containing glucose and casein but not fat was reduced after administration of the COOH-terminal octapeptide of cholecystokinin (CCK-8, 4 micrograms/kg ip). This decrease was antagonized by both asperlicin (10 mg/kg ip) and naloxone (0.1 mg/kg sc). Intracerebroventricular (icv) administration of an opiate antagonist that poorly crosses the blood-brain barrier, methyl levallorphan (10 micrograms/kg), did not modify gastric emptying of milk but accelerated it when peripherally administered (0.1 mg/kg sc). Similarly, asperlicin (icv) administered at a dose of 1 mg/kg did not affect milk emptying. These results indicate that endogenous opiates are involved at peripheral levels in the regulation of gastric emptying of fat meals only and that such regulation involves release of CCK.

Animals↗

PubMed1988

Role of motility in pathogenesis of constipation and diarrhea.

Several attempts have been made in order to classify the gastrointestinal motility disorders; they are mainly based upon the type of disorder in transit and the region of the gastrointestinal tract affected. Many digestive motor disturbances do not constitute entities, but are pathophysiologic mechanisms that may contribute to the production of symptoms and signs of various diseases. The abnormal interdigestive motility pattern or the migrating motor complex often corresponds to the absence of phase 3 and several observations strongly suggest that this disordered motility pattern is the cause rather than the consequence of intestinal bacterial overgrowth. Disturbances of colonic motility are often associated with diarrhea; however, the nature of motor alterations depends on the diarrheal disease (episodic, continuous with or without pain). Finally, both gastrointestinal and colonic motor disturbances may contribute to the pathogenesis of constipation and diarrhea; however, several findings suggest that colonic motor alterations are the consequence rather than the cause of changes in bowel habits.

Animals↗

PubMed1988

Effect of sennosides on colon motility in dogs.

Oral administration of sennosides (20-30 mg/kg) to fasted dogs has been shown to induce a strong and long-lasting inhibition of myoelectric colon activity which was evident after a delay of 6-10 h corresponding to oro-cecal transit and colonic metabolism and was accompanied by abundant diarrhea. When sennosides were given 1 h before a meal, the postprandial increase in colon motility failed to appear. Recent studies with strain gage transducers confirm the inhibition of colonic motility after oral sennosides but, in addition, 3-10 'giant contractions' with a high amplitude appeared during the period of inhibition. Most of these single contractions were propagated over the second half of the colon at a velocity of 0.5-2 cm/min. Elimination of liquid feces was always associated with giant contractions. These giant contractions have also been described with other stimuli (i.v. guanethidine or neostigmine, oral castor oil, intraluminal hypertonic glucose) and are therefore not specific for sennosides.

Animals↗

PubMed1988

Sennosides and human colonic motility.

The effects of stimulant laxatives on colonic motility in man still remain controversial. Stimulation of peristalsis or a decrease of intraluminal pressure has been described manometrically after intraluminal administration of laxatives including senna. In contrast to manometry, electromyographic methods using an endoluminal probe enable continuous colonic motor recordings over a long colonic segment for at least 24 h, and consequently studies following the course of laxative effects after oral administration, the classical therapeutic route, are possible. Preliminary results using sennosides obtained with few subjects provide evidence for an increase in propulsive activity expressed as an increased number of migrating long-spike bursts in the left and sigmoid human colon. This motor colonic pattern seems to be a common feature in nonspecific or induced diarrhoea.

Anthraquinones↗

PubMed1988

A simple double radiolabeled technique to evaluate gastric emptying of canned food meal in dogs. Application to pharmacological tests.

Simultaneous measurement of solid and liquid phases of gastric emptying for a standard canned food meal was performed using a double radiolabeled technique in six dogs equipped with gastric cannula. The liquid phase (100 ml of tap water containing [14C] polyethylene glycol 4000) was added to the solid phase (400 g of canned food containing 10 g of liver tagged with [57Co] cyanocobalamine) and was presented for spontaneous eating to the dog. Determinations of individual emptying curves for solid and liquid phases were performed by total collection of gastric contents at one hour intervals 1 to 4 h after feeding. Regression constants and correlation coefficients indicated that liquids evacuated as a logarithmic function of time while solids emptied linearly between 1 and 4 h after the meal. Using this method we showed that orally (PO) administered metoclopramide (1 mg/kg) and domperidone (5 mg/kg) increased emptying of liquid phase measured one hour after eating by 106.3 p. 100 and 59.4 p. 100, respectively, but did not modify that of solid phase; in contrast, cisapride (5 mg/kg PO) increased emptying of the solid and liquid phases at one hour by 41.5 p. 100 and 73.0 p. 100, respectively.

Animal Feed↗

PubMed1987

Reversal of the effects of centrally-administered morphine on colonic motility in dogs by the benzodiazepine receptor antagonist RO 15-1788.

The effects of intravenous (i.v.) and intracerebroventricular (i.c.v.) administration of morphine on jejunal and colonic motility were investigated in conscious dogs chronically prepared with strain gage transducers and compared to those of i.c.v. DAGO, a highly selective opiate mu agonist. Morphine i.v. (100 micrograms/kg) and i.c.v. (10 micrograms/kg) administered 3 hrs after a meal stimulated colonic motility for 3-5 hrs and induced a phase 3 on the jejunum, which appeared after a 15-60 min delay following i.c.v. administration. These effects were reproduced by DAGO administration at doses of 2 micrograms/kg i.v. and 0.2 micrograms/kg i.c.v. The effects of i.v., but not those of i.c.v., morphine and DAGO on jejunal and colonic motility were blocked by a previous administration of naloxone (100 micrograms/kg i.v.). The colonic stimulation but not the jejunal phase 3 induced by i.c.v. morphine and DAGO were blocked by RO 15-1788 (1 mg/kg i.v.), a selective benzodiazepine antagonist. The colonic stimulation induced by i.v. morphine or DAGO was not modify by i.v. RO 15-1788. It is concluded that i.c.v. administration of mu agonist involved benzodiazepine but not opiate receptors to stimulate colonic motility in dogs.

Animals↗

PubMed1987

Central muscarinic control of the pattern of small intestinal motility in rats.

The effects of central and peripheral administration of muscarinic agonists and antagonists on small intestinal motility were examined in conscious rats chronically fitted with electrodes implanted in the duodeno-jejunal wall and a cannula in a cerebral lateral ventricle. Intracerebroventricular (i.c.v.) administration of either atropine or pirenzepine at doses from 1 to 10 micrograms, 15 min before a 3 and 6 g lab chow meal significantly reduced the duration of the postprandial disruption of the migrating myoelectric complexes (MMC). The reduction was significantly greater for atropine, a mixed M1 and M2 muscarinic receptor antagonist, than for pirenzepine, an antagonist with a high affinity for M1 receptors. At a higher dose (10 micrograms) intra peritoneal (i.p.) administration of atropine or pirenzepine did not modify the postprandial disruption of MMC. Oxotremorine (10 ng) a M2 agonist, but not McNeil A343 (5 micrograms), a selective M1 agonist, given i.c.v. in fasted rats disrupted for 1.5 h the MMC pattern. At the same doses given i.p. oxotremorine and McNeil A343 disrupted the MMC for 15 and 45 min respectively. We conclude that the postprandial changes in the small intestinal motility involve muscarinic receptors, mainly of M2 subtype, at the level of the central nervous system.

Animals↗

PubMed1987

Histochemical characterization of glycoproteins present in jejunal and colonic goblet cells of pigs on different diets. A biopsy study using chemical methods and peroxidase-labelled lectins.

We examined the glycoprotein composition of intestinal goblet cells in jejunal and colonic biopsies obtained from pigs on different diets. Paraffin sections were stained both chemically and with the following horseradish-peroxidase conjugated lectins: Canavalia ensiformis (Con-A), Limulus polyphemus (LPA), Lotus tetragonolobus (LTA), Arachis hypogaea (PNA), Ricinus communis (RCA1), Glycine max (SBA) and Triticum vulgaris (WGA). Using chemical staining procedures, only small quantitative differences were noted between the two organs. With respect to lectin staining, the mucus of the jejunum was characterized by the absence of Con-A binding sites, and colonic mucus consistently exhibited an absence of SBA affinity. After dietary modifications, O-acetyl sialic acid reactivity was lowered in the jejunum but was enhanced in the colon. In the jejunum, the glycoproteins became neuraminidase susceptible, whereas the colon became characterized by the absence of neutral mucins. The affinity for the tested lectins after the different diets was variable, but the most striking effects were observed after the fibreless diet (milk alone). Our data suggest the existence of marked regional variations in goblet-cell mucus and indicate significant differences between the glycoprotein components of the jejunal and colonic mucosa. Furthermore, the biosynthesis of mucins in both regions was altered by even only short-term feeding modifications.

Animals↗

PubMed1987

Stimulation of gastrointestinal motility by loperamide in dogs.

The effects of loperamide on gastrointestinal motility were investigated in conscious fasted dogs chronically fitted with strain-gauge transducers on the antrum, the jejunum, and the colon. Oral administration of loperamide (0.1 mg/kg) induced, after a delay of 20-30 min, a long-lasting (8-12 hr) stimulation of gastrointestinal motility associated with a disorganization of the cyclic activity at the three levels investigated. These effects were reproduced by a subcutaneous administration at the same dose and were antagonized by previous intravenous administration of naloxone or a quaternary opiate antagonist. Intracolonic administration (0.1 mg/kg) stimulated, after a delay of 20-30 min, colonic motility only. Intracerebroventricular loperamide (1 microgram/kg) induced a long-lasting (15-20 hr) inhibition of the gastric motility and a short (2-hr) disorganization of the jejunal motor profile. These data show that oral loperamide stimulates gastrointestinal motility in dogs and involves peripheral opiate receptors.

Administration, Oral↗

PubMed1987

Influence of acoustic stress by noise on gastrointestinal motility in dogs.

The effects of acoustic stress (AS) on gastrointestinal motility and their prevention by previous treatment with naloxone, phentolamine, propranolol, muscimol, and diazepam were investigated in intact and vagotomized fasted dogs fitted with chronically implanted strain gauges on the antrum at 10 cm from pylorus and on the jejunum at 70 and 140 cm from the pylorus. These effects were compared to those produced by intracerebroventricular administration of ovine corticotropin releasing factor (oCRF). Beginning 40-50 min after the occurrence of a gastric migrating motor complex (MMC), a 1-hr hearing of prerecorded intense music through earpieces (less than 100 dB) delayed the occurrence of the next gastric MMC observed after 2.8 +/- 1.2 hr, while jejunal MMC were still present at a normal frequency. During AS, heart rate and plasma cortisol were significantly increased by 32.7 and 215%, respectively, 10-15 min after the beginning of hearing. The AS-induced lengthening of the gastric MMC cycle as well as cortisol increase were abolished after previous administration of diazepam (0.5 mg/kg intramuscular) or muscimol (10 micrograms/kg intravenous), while they were still present after naloxone (0.1 mg/kg intravenous), phentolamine (0.2 mg/kg intravenous), or propranolol (0.1 mg/kg intravenous). CRF administered intracerebroventricularly (100 ng/kg) also delayed the occurrence of gastric MMC without affecting jejunal motility, and this effect was not antagonized by previous treatment with diazepam or muscimol. Both the effects of AS and CRF were abolished after bilateral thoracic vagotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Effects of treatment with smectite on gastric and intestinal glycoproteins in the rat: a histochemical study.

A histochemical study was carried out to evaluate the changes that occur in the glycoproteins of the rat digestive tract following short term treatment with a clay smectite. Staining with the usual methods for detecting complex carbohydrates and with lectin conjugates (Con A, LTA, PNA, SBA and WGA) showed that the stomach was the susceptible organ. Increased staining with LTA and SBA, together with a decrease in the abundance of sulphate groups in the upper mucous neck cells, was observed after the clay treatment. Such treatment induced only slight changes in jejunal and colonic glycoproteins while no modification was observed in the colon. These data suggest that the content of mucus-producing cells could be affected by smectite, even following short-term treatment.

Animals↗