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Biomedical subjects

P Poitras

Publications and source records attributed to P Poitras.

At least 55 records · Page 3Linked to original sources

Effect of trimebutine on intestinal motility and plasma motilin in the dog.

In a previous report, trimebutine was shown to induce premature periods of phase III activity in fasting dogs, and its action was blocked by naloxone. In this study, we observed that trimebutine (5 mg X kg-1 iv) could induce premature phase IIIs in canine small intestine during interdigestive and digestive periods; trimebutine-induced phase IIIs were migrating along the small intestine faster than spontaneous activity fronts and; trimebutine-induced phase IIIs were accompanied by sharp rises in concentrations of plasma motilin. To further elucidate the trimebutine-stimulatory mechanism, we verified its effects on the release of various circulating peptides that influence intestinal motility: short-interval blood sampling during trimebutine infusion revealed that plasma motilin increases induced by trimebutine preceded the beginning of phase III in proximal duodenum; and gastrin and insulin postprandial releases were abolished by trimebutine. Therefore, trimebutine, by its simultaneous but opposite effects on various peptides that individually carry positive (e.g., motilin) or negative (e.g., gastrin and insulin) influences on the generation of activity fronts, could alter the equilibrium between stimulatory and inhibitory forces in such a way that, in some circumstances (e.g., postprandial period), stimulatory mechanisms become predominant.

Animals↗

Variations in plasma motilin, somatostatin, and pancreatic polypeptide concentrations and the interdigestive myoelectric complex in dog.

We have looked at the plasma concentrations of motilin, pancreatic polypeptide (PP), and somatostatin (STS) during the various phases of the interdigestive motor complex (IDMC) in dogs. As expected, motilin cyclical increase was always associated with the phase III of the IDMC. Statistical analysis of PP variations revealed a significant rise 10 min before duodenal phase III; however, in individual animals, this relationship was inconsistent. Although a dose-related increase in PP blood levels was induced by administration of synthetic canine motilin (0-200 ng kg-1 iv), fasting plasma levels of PP were not correlated with the concentrations of circulating endogenous motilin. After truncal vagotomy, while motilin release and the intestinal motility pattern remained unaltered, the phase III associated cyclical increases of PP disappeared. Infusion of physiological amounts of PP (1 microgram kg-1 h-1 for 3 h) mimicking the postprandial release failed to reproduce a fed pattern type of intestinal motility and of motilin secretion. No statistical correlation could be established between STS plasma levels and the motor activity of the intestine. STS plasma levels were not correlated with circulating concentrations of motilin and the exogenous administration of physiological doses of synthetic canine motilin failed to modify STS plasma levels. Morphine (200 micrograms kg-1 iv) stimulated only the release of motilin. These data suggest that the role played by circulating concentrations of PP and STS in the control of the IDMC in dog is at most minimal.

Animals↗

Motilin and the vagus in dogs.

The aim of this work was to determine the influence of the vagus on the circulating levels of immunoreactive (IR) motilin. Five mongrel dogs were equipped with chronically implanted electrodes in the small intestine to record the myoelectrical activity. The release of IR motilin during fasting, after a meal, and during an infusion of insulin was studied before and after truncal vagotomy at the diaphragmatic level. When tested at least two weeks after the operation, the motility pattern of the small intestine and the secretion of IR motilin remained unaltered by vagal section. Cyclic increases in IR motilin associated with phase III's of the interdigestive myoelectric complexes were still observed after vagotomy (maximum levels of IR motilin: 250 +/- 37 versus 239 +/- 19 fmol X mL-1, not significant), and they were still abolished by feeding or by insulin. However, an inhibitory influence can probably be mediated by the vagus since, in normal animals, vagal stimulation by a "modified sham feeding" (tease feeding or presentation of food) at the beginning of a period of phase III activity promptly interrupted this part of the complex and decreased significantly the release of IR motilin by about 20%. The release of motilin is not chronically altered by distal vagotomy in dogs.

Animals↗

Motilin is a digestive hormone in the dog.

In the fasting dog, plasma motilin levels fluctuate with the various phases of the interdigestive migrating complex. In this study, we present data supporting the hormonal status of motilin in the dog, as inducer of the phase III of the interdigestive migrating motor complex. Our argument is based on the following points: (a) synthetic canine motilin (200 ng/kg i.v.) reproducing physiological plasma increases of radioimmunoassayable motilin elicited, in the duodenum, activity fronts migrating aborally and absolutely similar to the phase III of the interdigestive migrating motor complex; (b) immunoneutralization of endogenous motilin by a specific motilin antiserum (7921) eliminated the occurrence of activity fronts in the proximal intestine. Migrating phase IIIs initiated below the ligament of Treitz were still documented, supporting again the existence of a motilin-independent mechanism inducing these fronts, which we have called "ectopic." We therefore believe that motilin can be considered a (inter)digestive hormone in the dog, having the physiological role of controlling the induction of the phase III of the interdigestive migrating complex in the proximal gut.

Action Potentials↗

Purification and characterization of canine intestinal motilin.

A 22 amino acid peptide with motilin-like immunoreactivity was purified from acetic acid extracts of small intestinal mucosa from mongrel dogs. Sequential chromatography on carboxymethyl-cellulose, Sephadex G-50, CM cellulose, Biogel P6, and two steps of high-performance liquid chromatography were used for purification. Microsequence analysis of the purified product permitted unambiguous identification of residues 2-22 as -VPIFTHSELQKIREKERNKGQ. The sequence of porcine intestinal motilin is FVPIFTYGELQRMQEKERNKGQ. The amino terminal residue of the canine peptide could not be assigned with certainty since Phe, Lys, and Ser all were identified by analysis of PTH derivatives on the first sequencing cycle. Definite amino acid differences between canine and porcine motilin thus were identified in positions 7, 8, 12, 13 and 14. These differences did not alter immunoreactivity of canine motilin with antibodies specific for the carboxyl-terminal portion of porcine motilin, but probably explain markedly diminished immunoreactivity with antibodies to the amino or mid-portion of porcine motilin. Synthetic Phe1 canine motilin was prepared by a solid phase method. The synthetic peptide had the same pattern of immunoreactivity as natural canine motilin and was biologically active with a potency similar to synthetic porcine motilin for induction of premature activity fronts of the interdigestive motor complex in the small intestine of fasting dogs.

Amino Acid Sequence↗

Stimulation of motilin release by bombesin in dogs.

Bombesin (BBS) was infused in conscious fasting dogs to document its effects on the release of motilin in the blood and on intestinal motility. When BBS was infused for 3 h (0.125 and 0.5 microgram X kg-1 X h-1), a specific pattern of myoelectric activity was induced: 1) the pacesetter potentials were increased in frequency but decreased in amplitude; 2) a moderate spike activity (weak phase II) was superimposed on this disorganized pacesetter activity, and activity fronts were abolished despite elevated motilin levels. A second experiment was performed in which motilin levels during BBS administration for a selected period of an interdigestive myoelectric complex (IDMC) could be compared with those obtained at a similar period of a preceding IDMC in which a saline solution had been infused. The motilin blood levels measured during BBS administration (0.25, 0.5, 1.0, and 2.0 micrograms X kg-1 X h-1 for 20 min each stepwise) were significantly higher than those obtained with saline. The administration of BBS synchronized with the IDMC was necessary to document its effect on motilin release, because when BBS was infused at an unknown period of the IDMC no rise of motilin levels over basal could be detected. Because of its contradictory effects on the release of motilin (stimulation of motilin release) and on the IDMC (inhibition of motilin effect), a physiological role of BBS as an endocrine regulator of motilin release is questionable. On the other hand, the possibility that BBS controls motilin release in a paracrine or neurocrine role cannot be excluded.

Action Potentials↗

Short-term treatment with sucralfate or cimetidine in gastric ulcer: preliminary results of a controlled randomized trial.

The aim of this study was to compare the healing capacities of sucralfate and cimetidine in gastric ulcer. Twenty-nine patients were randomly assigned to active sucralfate (1 g qid) and cimetidine placebo, or to cimetidine (300 mg qid) and sucralfate placebo. The patients were endoscoped before entry into the study, after 4 wk, and after 8 wk if complete healing was not found at 4 wk. Twenty-five patients completed the study. After 4 wk, 50% (6/12) of the sucralfate patients had healed in comparison to 54% (7/13) of cimetidine patients. After 8 wk, the cumulative healing rates were 75% and 77%, respectively. The results indicate that sucralfate is as effective as cimetidine in the short-term treatment of gastric ulcer.

Adult↗

Alkaline reflux gastritis: Roux-en-Y diversion is effective.

Even though controversy persists over the physiopathology of alkaline reflux gastritis, Roux-en-Y diversion is a well-accepted surgical treatment and was used in 23 patients over a 6-year period at the Hôpital St-Luc in Montreal. Of the 23 patients, 21 had complete relief of symptoms. Objective criteria for the selection of patients who would benefit from operation are still to be defined. The authors discuss the physiopathology through an extensive review of the literature.

Adult↗

Effect of a combination of gastrin, secretin, cholecystokinin, glucagon, and gastric inhibitory polypeptide on jejunal absorption in man.

In 11 conscious volunteers, the jejunal absorption was measured during basal state and during the simultaneous intravenous infusion of small doses of gastrin, secretin, cholecystokinin, glucagon and gastric inhibitory polypeptide. The blood levels of gastrin, secretin, glucagon, and GIP were measured by RIA and were close to those achieved after a meal. The basal net absorption of water and electrolytes was reversed to a net secretion during the hormonal infusion. These results suggest that the jejunal secretion observed after a meal in man may be mediated by hormones released by the meal.

Adolescent↗

Absence of effect of somatostatin on the guinea pig gallbladder.

The effect of somatostatin (GH-RIH) on cholecystokinin octapeptide (OP-CCK) or acetylcholine (ACh) induced contraction of the guinea pig gallbladder was evaluated in vitro. GH-RIH failed to inhibit the muscle contraction induced by OP-CCK or ACh. To correlate with the in vitro results, the effect of GH-RIH on OP-CCK induced contraction of the gallbladder was evaluated in the guinea pig in vivo. GH-RIH did not affect the OP-CCK induced contraction of the gallbladder. Our results suggest that GH-RIH does not have direct inhibitory effect on the contraction of the guinea pig gallbladder induced by OP-CCK or ACh.

Acetylcholine↗

Immunological and biological studies on cholecystokinin in rat brain.

Cholecystokinin-like immunoreactivity (CCK-LI) was demonstrated by radioimmunoassay in aqueous (n = 3) and acid (n = 10) extracts of cortex (42 +/- 9 pmol/g; 4.0 +/- 1.8 pmol/g), thalamus (4.1 +/- 1.1 pmol/g; 1.0 +/- 0.2 pmol/g), and hypothalamus (58 +/- 14 pmol/g; 6.3 +/- 0.7 pmol/g). Sephadex chromatography revealed that more than 95% of the immunoreactivity in acid extracts coeluted with CCK33 standard. In aqueous extracts more than 80% of immunoreactivity coeluted with CCK8 standard. Both the CCK33- and CCK8-like materials induced contraction of guinea pig gallbladder in vitro. L-Tryptophan (200 mg/kg) and high-dose morphine (20 mg/kg) decreased CCK33-LI concentrations in hypothalamus and thalamus. Low-dose morphine (5 mg/kg) decreased CCK33-LI in hypothalamus. We conclude that 1) CCK-LI is present in cortex, thalamus, and hypothalamus of the rat brain, 2) CCK-LI exists in two predominant molecular forms coeluting with CCK33 and CCK8, 3) both molecular forms are biologically active, and 4) concentrations of rat brain CCK33-LI are modulated by serotonergic and opiate mechanisms.

Animals↗