scholarly journals Cholinergic giant migrating contractions in conscious mouse colon assessed by using a novel noninvasive solid-state manometry method: modulation by stressors

2009 ◽  
Vol 296 (5) ◽  
pp. G992-G1002 ◽  
Author(s):  
G. Gourcerol ◽  
L. Wang ◽  
D. W. Adelson ◽  
M. Larauche ◽  
Y. Taché ◽  
...  

There is a glaring lack of knowledge on mouse colonic motility in vivo, primarily due to unavailability of adequate recording methods. Using a noninvasive miniature catheter pressure transducer inserted into the distal colon, we assessed changes in colonic motility in conscious mice induced by various acute or chronic stressors and determined the neurotransmitters mediating these changes. Mice exposed to restraint stress (RS) for 60 min displayed distal colonic phasic contractions including high-amplitude giant migrating contractions (GMCs), which had peak amplitudes >25 mmHg and occurred at a rate of 15–25 h−1 of which over 50% were aborally propagative. Responses during the first 20-min of RS were characterized by high-frequency and high-amplitude contractions that were correlated with defecation. RS-induced GMCs and fecal pellet output were blocked by atropine (0.5 mg/kg ip) or the corticotrophin releasing factor (CRF) receptor antagonist astressin-B (100 μg/kg ip). RS activated colonic myenteric neurons as shown by Fos immunoreactivity. In mice previously exposed to repeated RS (60 min/day, 14 days), or in transgenic mice that overexpress CRF, the duration of stimulation of phasic colonic contractions was significantly shorter (10 vs. 20 min). In contrast to RS, abdominal surgery abolished colonic contractions including GMCs. These findings provide the first evidence for the presence of frequent cholinergic-dependent GMCs in the distal colon of conscious mice and their modulation by acute and chronic stressors. Noninvasive colonic manometry opens new venues to investigate colonic motor function in genetically modified mice relevant to diseases that involve colonic motility alterations.

2002 ◽  
Vol 283 (3) ◽  
pp. G544-G552 ◽  
Author(s):  
Mona Li ◽  
Christopher P. Johnson ◽  
Mark B. Adams ◽  
Sushil K. Sarna

The aim of this study was to characterize in vivo rat colonic motor activity in normal and inflamed states and determine its neural regulation. Circular muscle contractions were recorded by surgically implanted strain-gauge transducers. The rat colon exhibited predominantly giant migrating contractions (GMCs) whose frequency decreased distally. Only a small percentage of these GMCs propagated in the distal direction; the rest occurred randomly. Phasic contractions were present, but their amplitude was very small compared with that of GMCs. Inflammation induced by oral administration of dextran sodium sulfate suppressed the frequency of GMCs in the proximal and middle but not in the distal colon. Frequency of GMCs was suppressed by intraperitoneally administered atropine and 4-diphenylacetoxy- N-methyl-piperidine methiodide and was enhanced by N w-nitro-l-arginine methyl ester. Serotonin, tachykinin, and calcitonin gene-related peptide receptor or receptor subtype antagonists as well as guanethidine and suramin had no significant effect on the frequency of GMCs. Verapamil transiently suppressed the GMCs. In conclusion, unlike the canine and human colons, the rat colon exhibits frequent GMCs and their frequency is suppressed in inflammation. In vivo GMCs are stimulated by neural release of acetylcholine that acts on M3 receptors. Constitutive release of nitric oxide may partially suppress their frequency.


2010 ◽  
Vol 298 (1) ◽  
pp. G45-G56 ◽  
Author(s):  
Lixin Wang ◽  
Guillaume Gourcerol ◽  
Pu-Qing Yuan ◽  
S. Vincent Wu ◽  
Mulugeta Million ◽  
...  

Peptide YY (PYY) antisecretory effect on intestinal epithelia is well established, whereas less is known about its actions to influence colonic motility in conscious animals. We characterized changes in basal function and stimulated colonic motor function induced by PYY-related peptides in conscious mice. PYY3–36, PYY, and neuropeptide Y (NPY) (8 nmol/kg) injected intraperitoneally inhibited fecal pellet output (FPO) per hour during novel environment stress by 90%, 63%, and 57%, respectively, whereas the Y1-preferring agonists, [Pro34]PYY and [Leu31,Pro34]NPY, had no effect. Corticotrophin-releasing factor 2 receptor antagonist did not alter PYY3–36 inhibitory action. PYY and PYY3–36 significantly reduced restraint-stimulated defecation, and PYY3–36 inhibited high-amplitude distal colonic contractions in restrained conscious mice for 1 h, by intraluminal pressure with the use of a microtransducer. PYY suppression of intraperitoneal 5-hydroxytryptophan induced FPO and diarrhea was blocked by the Y2 antagonist, BIIE0246, injected intraperitoneally and mimicked by PYY3–36, but not [Leu31,Pro34]NPY. PYY3–36 also inhibited bethanechol-stimulated FPO and diarrhea. PYY3–36 inhibited basal FPO during nocturnal feeding period and light phase in fasted/refed mice for 2–3 h, whereas the reduction of food intake lasted for only 1 h. PYY3–36 delayed gastric emptying after fasting-refeeding by 48% and distal colonic transit time by 104%, whereas [Leu31,Pro34]NPY had no effect. In the proximal and distal colon, higher Y2 mRNA expression was detected in the mucosa than in muscle layers, and Y2 immunoreactivity was located in nerve terminals around myenteric neurons. These data established that PYY/PYY3–36 potently inhibits basal and stress/serotonin/cholinergic-stimulated propulsive colonic motor function in conscious mice, likely via Y2 receptors.


2007 ◽  
Vol 292 (1) ◽  
pp. G419-G428 ◽  
Author(s):  
L. Wang ◽  
V. Martínez ◽  
H. Kimura ◽  
Y. Taché

Serotonin [5-hydroxytryptamine (5-HT)] acts as a modulator of colonic motility and secretion. We characterized the action of the 5-HT precursor 5-hydroxytryptophan (5-HTP) on colonic myenteric neurons and propulsive motor activity in conscious mice. Fos immunoreactivity (IR), used as a marker of neuronal activation, was monitored in longitudinal muscle/myenteric plexus whole mount preparations of the distal colon 90 min after an intraperitoneal injection of 5-HTP. Double staining of Fos IR with peripheral choline acetyltransferase (pChAT) IR or NADPH-diaphorase activity was performed. The injection of 5-HTP (0.5, 1, 5, or 10 mg/kg ip) increased fecal pellet output and fluid content in a dose-related manner, with a peak response observed within the first 15 min postinjection. 5-HTP (0.5–10 mg/kg) dose dependently increased Fos expression in myenteric neurons, with a maximal response of 9.9 ± 1.0 cells/ganglion [ P < 0.05 vs. vehicle-treated mice (2.3 ± 0.6 cells/ganglion)]. There was a positive correlation between Fos expression and fecal output. Of Fos-positive ganglionic cells, 40 ± 4% were also pChAT positive and 21 ± 5% were NADPH-diaphorase positive in response to 5-HTP, respectively. 5-HTP-induced defecation and Fos expression were completely prevented by pretreatment with the selective 5-HT4 antagonist RS-39604. These results show that 5-HTP injected peripherally increases Fos expression in different populations of cholinergic and nitrergic myenteric neurons in the distal colon and stimulates propulsive colonic motor function through 5-HT4 receptors in conscious mice. These findings suggest an important role of activation of colonic myenteric neurons in the 5-HT4 receptor-mediated colonic propulsive motor response.


2012 ◽  
Vol 302 (12) ◽  
pp. G1373-G1380 ◽  
Author(s):  
Etienne Suply ◽  
Philine de Vries ◽  
Rodolphe Soret ◽  
François Cossais ◽  
Michel Neunlist

Postnatal changes in the enteric nervous system (ENS) are involved in the establishment of colonic motility. In adult rats, butyrate induced neuroplastic changes in the ENS, leading to enhanced colonic motility. Whether butyrate can induce similar changes during the postnatal period remains unknown. Enemas (Na-butyrate) were performed daily in rat pups between postnatal day (PND) 7 and PND 17. Effects of butyrate were evaluated on morphological and histological parameters in the distal colon at PND 21. The neurochemical phenotype of colonic submucosal and myenteric neurons was analyzed using antibodies against Hu, choline acetyltransferase (ChAT), and neuronal nitric oxide synthase (nNOS). Colonic motility and neuromuscular transmission was assessed in vivo and ex vivo. Butyrate (2.5 mM) enemas had no impact on pup growth and histological parameters compared with control. Butyrate did not modify the number of Hu-immunoreactive (IR) neurons per ganglia. A significant increase in the proportion (per Hu-IR neurons) of nNOS-IR myenteric and submucosal neurons and ChAT-IR myenteric neurons was observed in the distal colon after butyrate enemas compared with control. In addition, butyrate induced a significant increase in both nitrergic and cholinergic components of the neuromuscular transmission compared with control. Finally, butyrate increased distal colonic transit time compared with control. We concluded that butyrate enemas induced neuroplastic changes in myenteric and submucosal neurons, leading to changes in gastrointestinal functions. Our results support exploration of butyrate as potential therapy for motility disorders in preterm infants with delayed maturation of the ENS.


2021 ◽  
Vol 5 (1) ◽  
Author(s):  
M. H. Vriesman ◽  
C. S. de Jonge ◽  
S. Kuizenga-Wessel ◽  
B. Adler ◽  
A. Menys ◽  
...  

Abstract Background Colonic manometry is the current reference standard for assessing colonic neuromuscular function in children with intractable functional constipation (FC). Recently, cine magnetic resonance imaging (cine-MRI) has been proposed as a non-invasive alternative. We compared colonic motility patterns on cine-MRI with those obtained by manometry in children, by stimulating high-amplitude propagating contractions (HAPCs) with bisacodyl under manometric control while simultaneously acquiring cine-MRI. Methods After Institutional Review Board approval, adolescents with FC scheduled to undergo colonic manometry were included. A water-perfused 8-lumen catheter was used for colonic manometry recordings. After an intraluminal bisacodyl infusion, cine-MRI sequences of the descending colon were acquired for about 30 min simultaneously with colonic manometry. Manometry recordings were analysed for HAPCs. MRI images were processed with spatiotemporal motility MRI techniques. The anonymised motility results of both techniques were visually compared for the identification of HAPCs in the descending colon. Results Data regarding six patients (three males) were analysed (median age 14 years, range 12–17). After bisacodyl infusion, three patients showed a total of eleven HAPCs with colonic manometry. Corresponding cine-MRI recorded high colonic activity during two of these HAPCs, minimal activity during seven HAPCs, while two HAPCs were not recorded. In two of three patients with absent HAPCs on manometry, colonic activity was recorded with cine-MRI. Conclusions Simultaneous acquisition of colonic cine-MRI and manometry in children with FC is feasible. Their motility results did not completely overlap in the identification of HAPCs. Research is needed to unravel the role of cine-MRI in this setting.


1992 ◽  
Vol 262 (1) ◽  
pp. G62-G68 ◽  
Author(s):  
S. K. Sarna

We investigated the effect of absorbable and nonabsorbable fluid perfusion and cleansing on colonic motor activity in eight intact conscious dogs. Each dog was instrumented with an indwelling catheter in the proximal colon and seven strain gauge transducers on the entire colon. After an overnight fast, a control recording was made for 3 h, followed by 3 h of perfusion and 3 additional h of postperfusion recording. Next day, a 3-h recording was made when the colon was empty. The colon exhibited normal migrating and nonmigrating motor complexes in the control uncleansed state. The perfusion of absorbable electrolyte or nonabsorbable Colyte solution immediately disrupted the migrating motor complexes and replaced them with almost continuous but irregular contractions at all recording sites. Both solutions significantly prolonged the mean and total duration per hour of contractile states in the proximal, middle, and distal colon. The dogs began to leak fluid stools in squirts approximately 40-80 min after the start of perfusion. This type of incontinence was not associated with any specific type of motor activity. Infrequently, giant migrating contractions occurred during perfusion and caused explosive diarrhea. The migrating motor complexes remained disrupted during the 3-h postperfusion period. However, on the next day, the empty colon exhibited normal migrating motor complexes. The frequency of giant migrating contractions during perfusion and in the empty colon was significantly greater than that in the normal uncleansed colon. The total duration per hour of colonic motor activity in the empty colon was also greater than that in the normal uncleansed colon. We conclude that excessive fluid in the colon significantly alters its motor pattern.(ABSTRACT TRUNCATED AT 250 WORDS)


Author(s):  
Phil G Dinning ◽  
Lukasz Wiklendt ◽  
Marcello C. Costa ◽  
Simon J. H. Brookes ◽  
Maureen Amicangelo ◽  
...  

Bisacodyl is a stimulant laxative often used in manometric studies of pediatric constipation to determine if it can initiate propulsive high amplitude propagating contractions. While the effects of bisacodyl infusion on colonic motility are well described, the effects of the drug on other regions of the gut after colonic infusion are not known. The aim of the present study was to characterize the effects of bisacodyl on both colonic and small bowel motility. Methods. Twenty seven children (9.3 + 1.2 years) undergoing simultaneous high resolution antroduodenal and colonic manometry were included. Small bowel and colonic motor patterns were assessed prior to and after colonic infusion of bisacodyl. Patients were divided into 2 groups; responders and non-responders based on the presence of high amplitude propagating contractions (HAPC) after bisacodyl infusion. Results. Nineteen patients were responders. 188 post-bisacodyl HAPCs were identified with a mean count of 10.4 ± 5.5 (range, 3 -22), at a frequency of 0.6 ± 0.2/min and mean amplitude of 119.8 ± 23.6 mmHg.No motor patterns were induced in the small bowel. However, in the 19 responders the onset of HAPCs was associated with a significant decrease in small bowel contractile activity. In the non-responders there was no detectable change in small bowel motility after bisacodyl infusion. Conclusion. Bisacodyl induced HAPCs are associated with a significant reduction in small bowel motility probably mediated by extrinsic sympathetic reflex pathways. This inhibition is potentially related to rectal distension, caused by the HAPC anal propulsion of colonic content.


1992 ◽  
Vol 263 (4) ◽  
pp. G518-G526 ◽  
Author(s):  
M. F. Otterson ◽  
S. K. Sarna ◽  
S. C. Leming ◽  
J. E. Moulder ◽  
J. G. Fink

The colonic motor effects of fractionated irradiation were studied in five conscious dogs. Seven colonic and two ileal strain gauge transducers were implanted. After control recordings, an abdominal dose of 250 cGy was administered three times a week on alternate days for three successive weeks (total dose 2,250 cGy). Recordings were then continued for 3 wk after the completion of radiation. Colonic giant migrating contractions (GMCs) occurred at a frequency of 0.15 +/- 0.05 contractions/h in the control state. Only one of these contractions (8.3%) originated in the small bowel and propagated into the colon. Abdominal field irradiation significantly increased the incidence of colonic GMCs to 0.51 +/- 0.11 contractions/h (P < 0.05). Fifty-four percent of GMCs originated in the small intestine. GMCs during the radiation schedule were associated with explosive diarrhea on seven occasions. Irradiation did not alter the frequency of colonic migrating motor complexes, but the mean duration of contractile states decreased in the middle and distal colon. Diarrhea occurred as early as the second dose of radiation. Pathological changes in the colon were correlated with motor activity. Both small intestinal and colonic GMCs reverted to control frequencies after cessation of radiation exposure. Abdominal irradiation significantly altered the contractile activity of the colon. These changes are associated with abdominal cramping and diarrhea.


1993 ◽  
Vol 264 (6) ◽  
pp. G1024-G1030 ◽  
Author(s):  
R. W. Summers ◽  
B. Hayek

The purpose of the study was to compare colonic motor patterns before and after a single abdominal dose of X-rays in dogs. Recordings were made from five serosally implanted strain gauges at equidistant intervals along the colon in seven dogs (2 dogs also had 2 jejunal electrodes and 1 had ileal electrodes). Control recordings were made for 3 h in the fasted state and daily for 2 wk after an absorbed X-ray dose of 938 cGy was delivered to the abdomen. The duration of migrating colonic motor complexes decreased from 7.2 +/- 0.5 to 3.9 +/- 0.4 min while the mean amplitude fell from 10.3 +/- 0.6 to 1.8 +/- 0.2 g (P < 0.05). The rate of nonmigrating colonic motor complex occurrence increased from 0.6 +/- 0.1 to 1.2 +/- 0.2 per hour (P < 0.05). Colonic giant migrating contractions were rarely observed during control recordings (2 in 80 h of recording). In contrast, repetitive clusters of giant contractions were observed 5-8 days after exposure in five of seven dogs (1.5/h) and were associated with restlessness, whining, and passage of diarrheal stools (sometimes bloody) with nearly every occurrence. The basic colonic motility patterns were less disrupted than were jejunal myoelectric patterns at the same irradiation dosage. However, the study demonstrates the important role of colonic giant migrating contractions in pathological diarrheal states such as irradiation injury.


1987 ◽  
Vol 252 (4) ◽  
pp. G447-G457 ◽  
Author(s):  
C. A. Maggi ◽  
S. Manzini ◽  
A. Meli

The response of the rat proximal colon to distension and drugs that interfere with intrinsic and extrinsic nerves was investigated in vivo (urethan anesthesia) and in vitro. Saline distension induced the appearance of a cyclic contractile activity that was slightly inhibited by atropine (ATRO) and enhanced by physostigmine. Hexamethonium increased the distension-induced motor activity. Topical tetrodotoxin (TTX), lidocaine, or procaine produced an increase in motility of the proximal colon. Isolated segments of the proximal colon exhibit a high-amplitude phasic contractile activity that was increased by stretching, transiently inhibited by ATRO, unaffected by hexamethonium, and increased by TTX. The effects of both ATRO and TTX were more evident at high- than low-resting tone. In the presence of ATRO plus guanethidine, field stimulation of the isolated rat proximal colon suppressed the spontaneous contractile activity of the preparations. These findings indicate that, in the proximal colon of urethan-anesthetized rats, a tonic discharge of intramural nonadrenergic noncholinergic neurons suppresses the inherent myogenic contractile activity of the smooth muscle cells. Extrinsic nervous supply plays a subsidiary role in maintaining colonic motility.


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