Biomedical subjects

M J Fargeas

Publications and source records attributed to M J Fargeas.

At least 37 records · Page 2Linked to original sources

PubMed1988

Central mu, delta- and kappa-opioid influences on intestinal water and electrolyte transport in dogs.

The effects of intracerebroventricular (i.c.v.) administration of opioid peptides with mu-(DAGO), mu- and delta-(DALAMIDE, DADLE) and kappa-(dynorphin) properties on normal and stimulated (cholera toxin) net fluxes of water, Na+ and K+ through a jejunal Thiry-Vella loop were investigated in conscious dogs. Basal net water absorption was slightly, but significantly (P less than 0.05) increased during i.c.v. infusion of DALAMIDE or DAGO (0.5 ng/kg/min) but not DADLE and dynorphin-(1-13) at the same rate; DALAMIDE and DAGO also markedly reduced (by 72.3 and 79.5% respectively) the secretory effects of cholera toxin (0.4 micrograms/ml). Similar effects were obtained with DALAMIDE and DAGO when injected i.c.v. as a bolus (100 ng/kg) prior to cholera toxin infusion; they were suppressed after i.v. pretreatment with naltrexone (0.3 mg/kg) but also with propranolol (0.2 mg/kg). In contrast, i.v. phentolamine (0.2 mg/kg) and bilateral truncal vagotomy, were unable to block their effects. These results suggest that Met-enkephalin can act centrally to affect intestinal transport of (i) water and (ii) electrolytes in dogs. They act probably at central mu-receptors which are involved in the regulation of intestinal secretion mediated through a central or peripheral beta-adrenergic pathway.

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↗

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

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

Action of T-2 toxin on gastrointestinal transit in mice: protective effect of an argillaceous compound.

Using sodium [51Cr]chromate as radiolabeled marker, gastrointestinal transit of a milk test meal was determined in mice receiving for 4 days T-2 toxin (1 mg/kg per day per os) alone or with a clay, smectite (2 g/kg per day), given according to four different procedures. Gastric emptying and small intestinal transit were significantly accelerated after the 1st T-2 administration and during the 4 days of treatment. When smectite was given together with the toxin with or without pretreatment by smectite alone for 2 days, the T-2 induced disturbances in gastrointestinal transit remained unchanged. A pretreatment by smectite for 4 days abolished the T-2 induced acceleration of gastric emptying but not of small intestinal transit. When T-2 was incubated with smectite for 24 h before oral administration, gastric emptying and small intestinal transit were not significantly accelerated.

Animals↗

PubMed1987

Involvement of alpha-1 and alpha-2 adrenoceptors in the postlaparotomy intestinal motor disturbances in the rat.

The effects of phentolamine, yohimbine and prazosin on laparotomy induced intestinal motor disturbances were studied in anaesthetised fasted rats previously equipped with electrodes, chronically implanted on the duodenum and jejunum. During continuous recording of interdigestive myoelectric activity, laparotomy under thiopental anaesthesia (Nesdonal 40 mg/kg ip) induced a primary phase of total inhibition of spiking activity lasting 26.1 +/- 1.3 min (mean +/- SE) followed by a period of disorganised activity, the first propagated migrating myoelectric complex (MMC) occurring 71.4 +/- 7.9 min after laparotomy. Phentolamine (3 mg/kg), or yohimbine (1 mg/kg) given im before laparotomy decreased by 48 and 49%, respectively, the duration of postsurgical inhibition, with a normal MMC pattern occurring immediately after. In contrast, there was only a shortening of the postlaparotomy initial inhibition of spiking activity after im prazosin (100 micrograms/kg), with a late (50-60 min) recovery of the MMC pattern. These results suggest that the initial inhibition of intestinal motility induced by laparotomy may involve alpha-1 and alpha-2 adrenoceptors, while the disruption of the MMC pattern is mainly caused by the activation of alpha-2 receptors.

Adrenergic alpha-Antagonists↗

PubMed1986

A tetrapeptide isolated from hamster embryo with central opiate properties on gastrointestinal motility but not on pain perception.

The effects of centrally administered kentsin (H-Thr-Pro-Arg-Lys-OH) on intestinal motility and on pain perception were investigated in rats chronically equipped with lateral ventricle catheters. Intestinal motility was recorded electromyographically from electrodes placed on the duodeno-jejunum; analgesia was evaluated by the hot-plate and tail-flick tests. Kentsin (4.0 ug/kg), injected intracerebroventricularly (ICV) 2 hours after the beginning of a meal, restores the "fasted" i.e. the migrating myoelectric complex of intestinal motility, while a 5 times higher dose administered subcutaneously was inactive. The ICV effect of kentsin was blocked by previous ICV administration of naloxone (400 ug/kg). In contrast, kentsin administered ICV (40 ug/kg) or SC (200 ug/kg) did not affect significantly (P greater than 0.05) the time latency in the two analgesic tests during 90 minutes after its administration and did not significantly modify the analgesic effects of (D5-Ala2, Met5) enkephalinamide. We conclude that kentsin when centrally administered acts on opiate receptors to alter gastrointestinal motility but without effects on pain perception.

Animals↗

PubMed1986

Central alpha 2-adrenergic control of the pattern of small intestinal motility in rats.

The effects of central and peripheral administration of alpha 2-adrenoceptor agonists and antagonists on small intestinal motility were examined in conscious rats chronically fitted with electrodes implanted in the duodenojejunal wall and a cannula placed in a cerebral lateral ventricle. In fasted rats, intracerebroventricular or intraperitoneal administration of clonidine (5 micrograms) immediately disrupted the migrating myoelectric complex pattern with a total inhibition of spiking activity during the first hour, followed by a period of irregular spiking activity for 2 h. The inhibition was abolished by previous intramuscular administration of yohimbine (600 micrograms), and the period of irregular activity was suppressed by intracerebroventricular yohimbine (30 micrograms). Naphazoline, an alpha 2-agonist that poorly crosses the blood-brain barrier, only inhibited spiking activity when administered intraperitoneally (1 microgram) and induced only a period of irregular spiking activity when administered intracerebroventricularly at the same dose. In fed rats, intracerebroventricular administration of yohimbine or phentolamine (30 micrograms), and to a lesser extent prazosin, restores a migrating myoelectric complex pattern typical of the fasted state. Peripheral administration of these three antagonists at a dose 20 times higher was ineffective. Finally, both feeding and central administration of alpha 2-agonists disrupt the migrating myoelectric complex pattern. Such pharmacologic data suggest a possible role of central alpha 2-adrenoceptors in the regulation of intestinal motility in rats.

Animals↗

PubMed1986

Effects of corticotropin-releasing factor on plasma motilin and somatostatin levels and gastrointestinal motility in dogs.

The effects of intracerebroventricular and intravenous administration of corticotropin-releasing factor (CRF) on gastrointestinal motility, motilin-induced gastric motor response, and plasma motilin and somatostatin levels were investigated in fasted dogs chronically prepared with strain gauge transducers on the antrum and proximal jejunum. Administered intracerebroventricularly at doses of 20 and 100 ng/kg in fasted dogs, CRF suppressed for 4-5 h the gastric cyclic migrating motor complex. A similar dose (100 ng/kg) administered intravenously was inactive. Corticotropin-releasing factor administration by the intravenous route at 100 ng/kg did not alter the cyclic plasma motilin and somatostatin variations associated with the cyclic gastric motor events. During the blockade of antral migrating motor complex induced by intracerebroventricular administration of CRF, cyclic peaks of plasma motilin were absent whereas those of somatostatin persisted. The gastrointestinal migrating motor complex induced by the intravenous administration of porcine motilin (0.25 microgram/kg) was abolished when motilin was injected 2 h after the intravenous administration of CRF (100 ng/kg), whereas a similar dose of CRF administered intracerebroventricularly did not abolish the antral and jejunal motor responses to motilin. It is concluded that in fasted dogs, CRF administered centrally affects the interdigestive gastric motility and the release of motilin but not that of somatostatin. These results also suggest that the intracerebroventricular CRF-induced blockade of motilin release is responsible for the inhibition of gastric migrating motor complex and circulating CRF is able to affect the gastric motor response to porcine motilin through a peripheral mechanism that does not involve somatostatin and motilin secretion.

Animals↗

PubMed1986

Effects of calcitonin and CGRP alone or in combination on food intake and forestomach (reticulum) motility in sheep.

The effects of intracerebroventricular (ICV) and intravenous (IV) administration of calcitonin and calcitonin gene-related peptide (CGRP) on feeding behavior and reticular motility were investigated in sheep. ICV calcitonin at a dose of 2 to 200 mU/kg reduced, in a dose-related manner, the immediate (0-60 min) food intake. The daily food intake was also significantly (p less than 0.05) decreased for doses up to 20 mU/kg, and the frequency of reticular contractions during the first hour of eating was decreased by 27.9%. Calcitonin at the highest IV dose (200 mU/kg) did not affect feeding behavior or reticular motility. In contrast, CGRP given ICV did not affect the first 3 hour period of food intake, while a significant increase (27.8%) in daily food intake was observed at a dose of 20 ng/kg despite immediate inhibitory effects on reticular frequency. No effect on feeding behavior and forestomach motility was noticed for a 25 times higher dose IV administered. Furthermore, CGRP given ICV (100 ng/kg) did not antagonize the immediate anorectic effects of calcitonin (200 mU/kg), although it delayed commencement of rumination and partially restored the daily food intake. These results suggest that calcitonin and CGRP play opposite roles in the central control of food intake in sheep, probably by acting on different brain structures, yet have a similar effect on reticular motility.

Animals↗

PubMed1985

Different targets for i.v. vs. i.c.v. administered morphine for its effect on colonic motility in dogs.

The effects of intracerebroventricular (i.c.v.) or intravenous (i.v.) administration of morphine on colonic motility were investigated in conscious dogs chronically fitted with a strain gauge transducer sutured to the serosa of the proximal colon. Morphine administered i.v. (100 micrograms/kg) or i.c.v. (10 micrograms/kg) induced similar increases in the motility index for about 3 h. The pattern of colonic contractions after i.v. morphine mainly consisted of an increase in the number of phases of contractile activity each lasting about 5 min. Morphine i.c.v. administered induced a peculiar pattern consisting of short (0.5-1.5 min) phases of contractile waves occurring at a high rate (10-15 per h). The effects of i.v. morphine were abolished after previous i.v. (1 microgram/kg) or i.c.v. (0.1 micrograms/kg) administration of naloxone or methyl-levallorphan, a narcotic antagonist with a high peripheral selectivity (100 micrograms/kg i.v., 10 micrograms/kg i.c.v.). The effects of i.c.v. morphine were not modified by previous i.v. or i.c.v. administration of naloxone (100 micrograms/kg). These results suggest that the stimulatory effect of i.v. morphine on colonic motility involves both central and peripheral components. The i.c.v. administration of morphine does not reproduce its central effect when given i.v. but acts on different central receptors.

Animals↗

PubMed1985

Enhancement of colonic motor response to feeding by central endogenous opiates in the dog.

The role of endogenous opiates in the colonic motor response to feeding has been investigated in four dogs chronically fitted with two strain gages on the proximal and distal colon and a cannula in cerebral lateral ventricle. A daily meal stimulated the colonic motility during 8-10 hrs. The colonic motility index was significantly higher during this period when an enkephalinase inhibitor, tiorphan, was intracerebroventricularly (i.c.v.) administered at a dose of 0.1 mg/kg before the meal. This effect was blocked by a previous i.c.v. administration of naltrexone (0.1 mg/kg) and reproduced by (D-Ala2, Met5) enkephalinamide (DALAMIDE) at a dose of 50 mg/kg. I.c.v. administration of tiorphan or DALAMIDE did not modify the colonic motility in dogs fasted for 48 hrs. The postprandial motility index remained unchanged after intravenous administration of tiorphan or DALAMIDE at the same dosages. These results provide evidence for a central control of the colonic motor response to feeding by endogenous enkephalins in dogs.

Animals↗

PubMed1985

Central control of intestinal motility by prostaglandins: a mediator of the actions of several peptides in rats and dogs.

The effect of intracerebroventricular and intravenous administrations of prostaglandin E2 on gastrointestinal motility were investigated in conscious rats and dogs using electrodes and strain gauges, respectively. Injections were performed during the fed state and the motor changes were compared with those after intracerebroventricular administration of calcitonin, neurotensin, and (D-Ala2, Met5) enkephalinamide. Intracerebroventricular administration of prostaglandin E2 (0.5 micrograms) to fed rats restored the migrating myoelectric complex for 67 +/- 16 min. A migrating myoelectric complex-restoring effect was also observed after intracerebroventricular administration of calcitonin (0.02 U) and neurotensin (80 ng). This effect was blocked by previous intracerebroventricular administration of indomethacin (0.25 mg). Administered centrally to dogs but not intravenously at a 10-fold greater dose, prostaglandin E2 (0.1 microgram/kg) reduced (52.8%) the duration of the jejunal postprandial motor state similarly to that observed after intracerebroventricular administration of calcitonin (0.1 U/kg), neurotensin (0.1 microgram/kg), and (D-Ala2, Met5) enkephalinamide (0.1 microgram/kg). These effects of calcitonin and neurotensin were abolished 4 h after an intramuscular injection of indomethacin (2 mg/kg), whereas those of (D-Ala2, Met5) enkephalinamide persisted. These results suggest that (a) prostaglandins act centrally to control the pattern of intestinal motility in both rats and dogs and (b) calcitonin and neurotensin when injected intracerebroventricularly affect the intestinal motor profile probably by stimulating prostaglandin release within the brain.

Action Potentials↗

PubMed1985

Central and peripheral control of gastrointestinal and colonic motility by endogenous opiates in conscious dogs.

The effects of two enkephalin analogues, (D-Ala2, Met5) and (D-Ala2, D-Leu5) enkephalinamide, on gastrointestinal and colonic motility were investigated in conscious fasted and fed dogs using chronically implanted strain gauges. The drugs, abbreviated here with the names DALAMIDE and DADLE, respectively, were administered by using both the intracerebroventricular and intravenous routes at increasing doses. In fasted dogs when administered via the intracerebroventricular route at a dose of 20 ng X kg-1, DALAMIDE disrupted the migrating myoelectric complex pattern. A similar effect was obtained only with a dose 25 times higher (500 ng X kg-1) administered intravenously; at this dosage DALAMIDE administered intravenously also reduced the colonic motility index by 66%. When intracerebroventricularly administered in fed dogs, 2 h after a meal, DALAMIDE (20 ng X kg-1) inhibited gastric motility but restored the jejunal migrating myoelectric complex pattern as "ectopic" complexes for 4-6 h. This effect however was not reproduced by intravenous treatment even at the highest dose used (500 ng X kg-1). Both intracerebroventricular and intravenous administration of DADLE, at doses as high as 100 and 500 ng X kg-1, respectively, affected neither the motility pattern nor the motility index of the antrum and proximal jejunum in the fasted or fed state. However, intracerebroventricular, but not intravenous, administration produced a short (10-15 min) increase of colonic motility. These results suggest that (a) Met-enkephalin influences the gastrointestinal motility predominately by a central action, manifested as a migrating myoelectric complex "reorganizing" effect in fed dogs; (b) Leu-enkephalin exerts a predominately centrally mediated stimulation of colonic motility, whereas Met-enkephalin inhibits it probably by a peripheral mechanism.

Animals↗

PubMed1985

Central actions of calcitonin on body temperature and intestinal motility in rats: evidence for different mediations.

The effects of intracerebroventricular (i.c.v.) administration of calcitonin and PGE2 on intestinal motility and body temperature were examined in conscious rats chronically fitted with intraparietal electrodes in the small intestine, a cannula in a cerebral lateral ventricle and a subcutaneous thermistor probe. Both calcitonin and PGE2 restored the fasted pattern of intestinal motility in fed rats and induced an increase in body temperature. Indomethacin, an inhibitor of the cyclooxygenase with calcium antagonistic properties, and TMB-8, an intracellular calcium antagonist, blocked the effects of calcitonin on intestinal motility and body temperature. Piroxicam, an inhibitor of the cyclooxygenase which does not affect calcium uptake blocked the thermic but not the intestinal effects of calcitonin. TMB-8 but not indomethacin or piroxicam partially blocked the effects of PGE2 on both intestinal motility and body temperature. It is concluded that the central hyperthermic effect of calcitonin is mediated through the formation and the release of prostaglandins whereas the central action of calcitonin on digestive motility results from intracerebral effects on calcium fluxes.

Animals↗

PubMed1985

Neurotensin: a central neuromodulator of gastrointestinal motility in the dog.

The effects of intracerebroventricular and intravenous injection of neurotensin on gastrointestinal and colonic motility were examined in fasted and fed conscious, intact, and vagotomized dogs. When administered intracerebroventricularly at 20 ng X kg-1 or higher doses in the fasted state, neurotensin reduced the duration of the periods of gastric motility for 3-4 h. During this time the jejunal migrating motor complex was replaced by isolated phases of regular activity occurring at a rhythm of 2-3/h, while colonic motility was unaffected. These effects were abolished after vagotomy and were not observed for 25 times higher doses when administered intravenously. Injected intracerebroventricularly at a dose of 100 ng X kg-1 30 min after a meal, neurotensin significantly reduced (P less than 0.01) the duration of the fed pattern (2.7 +/- 0.7 vs. 8.7 +/- 1.2 h for control); this effect was not observed when neurotensin was administered intracerebroventricularly 20 min before or 120 min after a meal or when injected intravenously. Systemic administration of neurotensin at a dose of 500 ng X kg-1 significantly increased (P less than 0.05) during 2 h the colonic motility indexes in both fasted and fed dogs before and after vagotomy. It is concluded that neurotensin can act i) centrally to control the pattern of antral and jejunal motility in the fasted and fed dogs, these effects being mediated by the vagus; and ii) peripherally to control the pattern of colonic motility, this response being unaffected by vagotomy.

Animals↗

PubMed1984

Prostaglandin E2: a neuromodulator in the central control of gastrointestinal motility and feeding behavior by calcitonin.

Two micrograms of prostaglandin E2 injected into the lateral ventricle of the brain in rats had the same anorectic and gastrointestinal motor effect as central administration of 0.02 unit of calcitonin. The effects of calcitonin were blocked by a previous intracerebroventricular administration of 0.25 milligram of indomethacin. These results suggest that both anorectic and gastrointestinal motor effects of calcitonin are centrally mediated by the release of prostaglandins.

Animals↗