Motilin and the postprandial motility of the antrum

1992 ◽  
Vol 70 (11) ◽  
pp. 1491-1495 ◽  
Author(s):  
M. Boivin ◽  
M. Riberdy ◽  
M. -C. Raymond ◽  
L. Trudel ◽  
P. Poitras
Keyword(s):  
Contractile Response ◽  
Plasma Concentrations ◽  
Phase Iii ◽  
Gastrointestinal Hormone ◽  
Postprandial Period ◽  
Postprandial Motility ◽  
Smooth Muscle Function ◽  
Plasma Motilin ◽  
Erythromycin Lactobionate ◽  
Motilin Receptor

This study was designed to establish whether the rise in plasma motilin observed after a meal in humans can influence the postprandial motor activity of the antrum. Antroduodenal postprandial motility profiles and indices obtained from 5 controls and 5 subjects infused with exogenous synthetic motilin (0.1 μg∙kg−1) or with the motilin receptor agonist erythromycin lactobionate (200 mg) were compared. Motilin infusion increased plasma motilin concentrations about 5 times above the physiological range but failed to modify the normal postprandial contractile response. On the other hand, in 4 of the 5 subjects, erythromycin induced an intense motor response that mimicked phase III of the migrating motor complex. Our study demonstrates that, during the postprandial period, motilin antral receptors can be stimulated only with doses of motilin exceeding the physiological plasma concentrations, and that the motor effect obtained did not mimic the usual postprandial motility pattern. Our results, therefore, do not support the proposal that the postprandial motility of the antrum is regulated by the plasma levels of motilin.Key words: antral motility, gastrointestinal hormone, gastrointestinal motility, motilin, regulatory peptide, smooth muscle function.

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

1986 ◽  
Vol 251 (3) ◽  
pp. G349-G353 ◽  
Author(s):  
P. Poitras ◽  
C. Honde ◽  
J. Havrankova ◽  
R. G. Lahaie ◽  
L. Trudel ◽  
...  
Keyword(s):  
Small Intestine ◽  
Spontaneous Activity ◽  
Intestinal Motility ◽  
Short Interval ◽  
Blood Sampling ◽  
Phase Iii ◽  
Postprandial Period ◽  
Proximal Duodenum ◽  
Plasma Motilin

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.

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

1985 ◽  
Vol 63 (12) ◽  
pp. 1495-1500 ◽  
Author(s):  
P. Poitras ◽  
M. Lemoyne ◽  
D. Tasse ◽  
L. Trudel ◽  
T. Y. Yamda ◽  
...  
Keyword(s):  
Pancreatic Polypeptide ◽  
Plasma Levels ◽  
Intestinal Motility ◽  
Plasma Concentrations ◽  
Statistical Correlation ◽  
Significant Rise ◽  
Phase Iii ◽  
Blood Levels ◽  
Plasma Motilin ◽  
Related Increase

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 μg 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 μg 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.

Effect of chronic hypoxia on myometrial responsiveness in the pregnant rat

1996 ◽  
Vol 270 (3) ◽  
pp. E477-E482 ◽  
Author(s):  
J. W. Rhee ◽  
L. D. Longo ◽  
W. J. Pearce ◽  
N. H. Bae ◽  
G. J. Valenzuela ◽  
...  
Keyword(s):  
Binding Sites ◽  
Chronic Hypoxia ◽  
Contractile Response ◽  
Plasma Concentrations ◽  
Hypoxic Exposure ◽  
Normal System ◽  
Pregnant Rat ◽  
Near Term ◽  
Air Control

Mechanisms involving the timing of normal parturition are not well understood in most animal species. To gain a greater understanding of the mechanisms, we employed hypoxia to perturb the normal system of parturition. The present study was designed to investigate the effects of chronic hypoxia on myometrial contractility in the near-term pregnant rat. Rats were exposed to room air (control) or to continuous hypoxia (10.5% O2) either from experimental days 19 through 21 (2-day exposure) or from experimental days 15 through 21 (6-day exposure). On day 21, blood was collected for hormone assays, and the uterine horns were collected from each dam. One horn was snap-frozen in liquid nitrogen for oxytocin (OT) receptor analysis, and the other was used for in vitro assessment of myometrial contractile responses to cumulative doses of OT or arginine vasopressin (AVP). Hypoxic exposure resulted in approximately 60% reduction of the maximal myometrial contractile response to OT and a significant reduction in OT binding sites from 256.9 +/- 34.9 to 84.9 +/- 21.3 fmol/mg protein (P<0.01). In contrast, the contractile response to AVP was unaffected after exposure to chronic hypoxia (P> 0.05). Additionally, we observed no difference in the plasma concentrations of estrogen, progesterone, and corticosterone. We conclude that chronic hypoxia decreased the effectiveness of OT-specific contractile mechanisms, at least partially through a decrease in OT binding sites.

scholarly journals Homeostatic and therapeutic roles of VIP in smooth muscle function: myo-neuroimmune interactions

2009 ◽  
Vol 297 (4) ◽  
pp. G716-G725 ◽  
Author(s):  
Xuan-Zheng Shi ◽  
Sushil K. Sarna
Keyword(s):  
Smooth Muscle ◽  
Inflammatory Response ◽  
Muscle Function ◽  
Contractile Response ◽  
Enteric Neurons ◽  
Muscle Dysfunction ◽  
Spontaneous Release ◽  
Circular Smooth Muscle ◽  
Smooth Muscle Function ◽  
Smooth Muscle Dysfunction

We tested the hypothesis that spontaneous release of vasoactive intestinal peptide (VIP) from enteric neurons maintains homeostasis in smooth muscle function in mild inflammatory insults and that infusion of exogenous VIP has therapeutic effects on colonic smooth muscle dysfunction in inflammation. In vitro experiments were performed on human colonic circular smooth muscle tissues and in vivo on rats. The incubation of human colonic circular smooth muscle strips with TNF-α suppressed their contractile response to ACh and the expression of the pore-forming α1C subunit of Cav1.2 channels. VIP reversed both effects by blocking the translocation of NF-κB to the nucleus and its binding to the κB recognition sites on hα1C1b promoter. The translocation of NF-κB was inhibited by blocking the degradation of IκBβ. Induction of inflammation by a subthreshold dose of 17 mg/kg trinitrobenzene sulfonic acid (TNBS) in rats moderately decreased muscularis externa concentration of VIP, and it had little effect on the contractile response of circular smooth muscle strips to ACh. The blockade of VIP and pituitary adenylate cyclase-activating peptide receptors 1/2 during mild inflammatory insult significantly worsened the suppression of contractility and the inflammatory response. The induction of more severe inflammation by 68 mg/kg TNBS induced marked suppression of colonic circular muscle contractility and decrease in serum VIP. Exogenous infusion of VIP by an osmotic pump reversed these effects. We conclude that the spontaneous release of VIP from the enteric motor neurons maintains homeostasis in smooth muscle function in mild inflammation by blocking the activation of NF-κB. The infusion of exogenous VIP mitigates colonic inflammatory response and smooth muscle dysfunction.

Intragastric monosodium l-glutamate stimulates motility of upper gut via vagus nerve in conscious dogs

2010 ◽  
Vol 298 (4) ◽  
pp. R1125-R1135 ◽  
Author(s):  
Yoshitaka Toyomasu ◽  
Erito Mochiki ◽  
Mitsuhiro Yanai ◽  
Kyoichi Ogata ◽  
Yuichi Tabe ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Vagus Nerve ◽  
Contractile Response ◽  
Conscious Dogs ◽  
Gut Motility ◽  
Umami Taste ◽  
Force Transducers ◽  
Postprandial Motility ◽  
Gastric Corpus ◽  
Pavlov Pouch

Monosodium l-glutamate (MSG) is a substance known to produce the umami taste. Recent studies indicate that MSG also stimulates a variety of activities in the gastrointestinal tract through its receptor in the gut, but no study has reported the activity in conscious large experimental animals. The aim of our study was to investigate whether direct intragastric MSG stimulates gut motility and to identify the mechanism in conscious dogs. Contractile response to intraluminal injection of MSG was studied in the fed and fasted states by means of chronically implanted force transducers. MSG (5, 15, 45, and 90 mM/kg) dissolved in water was injected into the stomach and duodenum in normal and vagotomized dogs. MSG solution was administered into the stomach before feeding, and gastric emptying was evaluated. Several inhibitors of gastrointestinal motility (atropine, hexamethonium, and granisetron) were injected intravenously before MSG administration to the stomach. The effect of MSG was investigated in Pavlov (vagally innervated corpus pouch), Heidenhain (vagally denervated corpus pouch), and antral pouch (vagally innervated) dogs. Upper gut motility was significantly increased by intragastric MSG but not significantly stimulated by intraduodenal MSG. Intragastric MSG (45 mM/kg) stimulated postprandial motility and accelerated gastric emptying. MSG-induced contractions were inhibited by truncal vagotomy, atropine, hexamethonium, and granisetron. Gut motility was increased by intrapouch injection of MSG in the Pavlov pouch, but it was not affected in the Heidenhain or antral pouch dogs. We conclude that intragastric MSG stimulates upper gut motility and accelerates gastric emptying. The sensory structure of MSG is present in the gastric corpus, and the signal is mediated by the vagus nerve.

Relationship of plasma motilin concentration to fat ingestion, duodenal acidification and alkalinization, and migrating motor complexes in dogs

1981 ◽  
Vol 59 (2) ◽  
pp. 180-187 ◽  
Author(s):  
J. E. T. Fox ◽  
N. S. Track ◽  
E. E. Daniel
Keyword(s):  
Species Difference ◽  
Maximal Activity ◽  
Significant Rise ◽  
Migrating Motor Complex ◽  
Phase Iii ◽  
Complex Activity ◽  
Duodenal Motility ◽  
Motor Complex ◽  
Duodenal Acidification ◽  
Plasma Motilin

Plasma motilin concentrations were measured in dogs following duodenal acidification and alkalinization and gastric instillation of fat. Antral and duodenal motility were recorded concurrently using intraluminal manometry. Alkalinization of the duodenum produced an increase in antral and duodenal motility and a significant rise in plasma motilin. Alkaline infusions at 5 mL/min into the duodenum initiated phase III of a migrating motor complex both in the antrum and in the duodenum. Duodenal acid infusions produced no change in plasma motilin concentrations while inhibiting antral motility and stimulating duodenal motility for the duration of the infusion. Gastric instillation of 60 g fat produced a 25% increase above basal motilin levels at 50 min after instillation. Motilin levels monitored during spontaneous migrating motor complexes showed peak motilin levels occurring during maximal activity of the antral duodenal region in seven out of nine motor complexes examined but motilin peaks also occurred without migrating complexes being present in this area and, as well, complexes occurred when motilin was undetectable. These results taken together with our other studies in man confirm that a true species difference exists between man and dog in the hormonal motor response to duodenal alkalinization. Although a relationship appears to exist between the appearance of maximal migrating motor complex activity in the gastroduodenal area and plasma motilin concentrations in dogs as in humans, the motilin peaks are probably neither necessary nor sufficient to induce phase III activity.

Small intestinal dysmotility in cirrhotic patients: correlation with severity of liver disease and cirrhosis-associated complications

2020 ◽  
Author(s):  
Felix Gundling ◽  
Margo Luxi ◽  
Holger Seidel ◽  
Wolfgang Schepp ◽  
Thomas Schmidt
Keyword(s):  
Visual Analysis ◽  
Phase Iii ◽  
Healthy Controls ◽  
Motor Patterns ◽  
Postprandial Motility ◽  
Intestinal Dysmotility ◽  
Computer Aided Analysis ◽  
Cirrhotic Patients ◽  
Small Intestinal ◽  
Small Bowel Manometry

Abstract Introduction Altered small intestinal motility has been observed in various manometry studies in patients with cirrhosis. Since small bowel manometry is available only in a few centers, interpretation of dysmotility in cirrhosis is controversial. Patients and Methods In this study, both fasting and postprandial manometric tracings of 24-hour antroduodenojejunal manometries were analyzed using both visual analysis and computer-aided analysis. Results In 34 patients (83 %), the mean migrating motor complex (MMC) cycle length was different compared with healthy controls. Phase II was prolonged in 27 patients (66 %), while phase I showed a reduced duration in 23 (56 %) and in phase III in 13 individuals (32 %). We also observed special motor patterns, e. g., migrating clustered contractions (MCCs) or retrograde clustered contractions (RCCs), which were present during fasting (69 %) and postprandial (92 %) motility, while none of the healthy controls showed any special motor patterns. Special motor patterns showed a significant correlation with the severity of cirrhosis (Child-Score; p > 0.05) and the existence of ascites (p < 0.05). Discussion This study in a large cohort of patients with cirrhosis by using 24-hour, solid state portable manometry showed in most individuals disturbances of cyclic fasting motility. Special motor patterns like RCCs during fasting and postprandial motility could be observed exclusively in the cirrhosis group, showing a significant correlation with severity of cirrhosis and the occurence of associated complications.

Five-year administration of fenretinide: pharmacokinetics and effects on plasma retinol concentrations.

1993 ◽  
Vol 11 (10) ◽  
pp. 2036-2042 ◽  
Author(s):  
F Formelli ◽  
M Clerici ◽  
T Campa ◽  
M G Di Mauro ◽  
A Magni ◽  
...  
Keyword(s):  
Plasma Levels ◽  
High Performance ◽  
Plasma Concentrations ◽  
Nipple Discharge ◽  
Treatment Interruption ◽  
Phase Iii ◽  
Breast Cancer Patients ◽  
Plasma Retinol ◽  
Drug Plasma Levels ◽  
Level Reduction

PURPOSE Monitoring of fenretinide (4HPR) levels, kinetics, and effects on retinal was performed in patients who participated in a phase I trial and who continued to be treated for 5 years as phase III trial patients. Accumulation of 4HPR in the breast was also assessed. PATIENTS AND METHODS Plasma concentrations of 4HPR, of its main metabolite N-(4-methoxyphenyl)retinamide (4MPR), and of retinol were assayed by high-performance liquid chromatography (HPLC) in breast cancer patients treated orally with 4HPR 200 mg/d for 5 years with a 3-day drug interruption at the end of each month. RESULTS 4HPR, at 200 mg/d, resulted in average 4HPR plasma levels of approximately 1 mumol/L, which remained steady and caused steady retinol level reduction; 4MPR levels, similar to those of 4HPR, slightly but significantly increased during the first 35 months, but at 5 years they were similar to those at 5 months. During daily treatment, baseline retinol concentrations were reduced by 71%; after a 3-day drug interruption, all patients recovered and the mean reduction was 38%. After discontinuation of 5-year treatment, 4HPR and 4MPR half-lives (t1/2 beta) were 27 and 54 hours, respectively, similar to those reported after 28 daily treatments. After 6 and 12 months, the concentrations of 4HPR were at the limit of detectability (0.01 mumol/L), whereas those of 4MPR were five times higher. Baseline retinol concentrations were already recovered after 1 month. Accumulation of this retinoid in the breast was evidenced by concentrations of 4HPR and 4MPR in nipple discharge and in breast biopsies that were 10 and 20 times higher, respectively, than those found in plasma. CONCLUSION 4HPR, at 200 mg/d for 5 years, resulted in constant drug plasma levels and constant retinol level reduction. After treatment interruption, 4HPR plasma concentrations decreased at the limit of detectability at 6 months and baseline retinol plasma concentrations were recovered after 1 month.

Human pancreatic secretion during phase II antral motility of the interdigestive cycle

1988 ◽  
Vol 254 (2) ◽  
pp. G249-G253 ◽  
Author(s):  
P. Layer ◽  
A. T. Chan ◽  
V. L. Go ◽  
E. P. DiMagno
Keyword(s):  
Phase Ii ◽  
Pancreatic Secretion ◽  
Plasma Concentrations ◽  
Close Correlation ◽  
Duodenal Motility ◽  
Healthy Humans ◽  
Cholinergic Tone ◽  
Plasma Motilin ◽  
Human Pancreatic Polypeptide ◽  
Interdigestive Motility

We determined if changes in the irregular motor activity of phase II, the dominant motility phase in awake fasting humans, are associated with fluctuations in pancreatic secretion by intubating the upper gastrointestinal tract of 15 healthy humans and recording antral and duodenal motility and obtaining duodenal samples for one or two interdigestive motility cycles. Antral phase II activity was graded as having low, intermediate, or high frequency of contractions and related to duodenal trypsin output and plasma concentrations of motilin and human pancreatic polypeptide (HPP), a marker of vagal cholinergic tone. Low, intermediate, and high phase II motor activities were significantly associated with trypsin outputs (U/10 min; mean +/- SE) of 576 +/- 137, 1,441 +/- 225, and 3,621 +/- 521, respectively (P less than 0.001). Plasma motilin levels did not vary with the grades of phase II motility (P greater than 0.1), but levels of plasma HPP and the grades of phase II motility were positively correlated (P less than 0.001). The close correlation among motility, pancreatic secretion, and plasma HPP during phase II suggests that vagal cholinergic pathways are involved in the common regulatory mechanism controlling phase II interdigestive motility and pancreatic secretion.

scholarly journals Motilin Comparative Study: Structure, Distribution, Receptors, and Gastrointestinal Motility

2021 ◽  
Vol 12 ◽  
Author(s):  
Takio Kitazawa ◽  
Hiroyuki Kaiya
Keyword(s):  
Endocrine Cells ◽  
Phase Iii ◽  
Regulatory Function ◽  
Experimental Conditions ◽  
Important Regulator ◽  
Hunger Signal ◽  
Interdigestive Migrating Motor Complex ◽  
Motilin Receptor ◽  
The Brain ◽  
Gi Motility

Motilin, produced in endocrine cells in the mucosa of the upper intestine, is an important regulator of gastrointestinal (GI) motility and mediates the phase III of interdigestive migrating motor complex (MMC) in the stomach of humans, dogs and house musk shrews through the specific motilin receptor (MLN-R). Motilin-induced MMC contributes to the maintenance of normal GI functions and transmits a hunger signal from the stomach to the brain. Motilin has been identified in various mammals, but the physiological roles of motilin in regulating GI motility in these mammals are well not understood due to inconsistencies between studies conducted on different species using a range of experimental conditions. Motilin orthologs have been identified in non-mammalian vertebrates, and the sequence of avian motilin is relatively close to that of mammals, but reptile, amphibian and fish motilins show distinctive different sequences. The MLN-R has also been identified in mammals and non-mammalian vertebrates, and can be divided into two main groups: mammal/bird/reptile/amphibian clade and fish clade. Almost 50 years have passed since discovery of motilin, here we reviewed the structure, distribution, receptor and the GI motility regulatory function of motilin in vertebrates from fish to mammals.

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