Cholinergic and nitrergic regulation of in vivo giant migrating contractions in rat colon

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.

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)


1989 ◽  
Vol 257 (5) ◽  
pp. G830-G835 ◽  
Author(s):  
S. K. Sarna ◽  
I. M. Lang

We investigated the effects of ingestion of a meal on colonic motor activity in six conscious dogs, each instrumented with seven strain-gauge transducers to record circular muscle contractions. A 1,300-kcal meal was given after a 4-h control recording. The post-prandial period of 8 h was subdivided into an early period lasting 2 h and a late period lasting 6 h. The ingestion of the meal did not disrupt the colonic migrating myoelectric complexes (CMMCs) but prolonged their cycle length in the early postprandial period. The cycle length was not different from the control during the late postprandial period. The mean and total duration of contractile activity per hour increased significantly during the early postprandial period in the distal colon but not in the proximal or the middle colon. During the late postprandial period the mean and total duration of contractile activity per hour increased significantly throughout the colon. Giant migrating contractions occurred rarely during the 8-h postprandial period. We conclude that different parts of the colon respond to the ingestion of a meal in different ways. The response also depends on whether the fresh digesta has reached the colon. The late postprandial response is likely to be due to the entry of fresh digesta into the colon.


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.


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.


1988 ◽  
Vol 66 (3) ◽  
pp. 359-368 ◽  
Author(s):  
T. Gonda ◽  
E. E. Daniel ◽  
F. Kostolanska ◽  
M. Oki ◽  
J. E. T. Fox

The responses of strips of the canine colon to stimulation of intrinsic nerves and to the probable mediators of these nerves were studied in vitro. Studies were carried out using longitudinal and circular muscle strips from proximal and distal colon with field stimulation and addition of agents to the bath. Overall, these and other studies in vivo suggested that acetylcholine was an ubiquitous mediator of neural excitation. Norepinephrine had mixed inhibitory and excitatory effects, the latter only in circular muscle. Inhibitory effects of norepinephrine seemed to be both pre- and post-synaptic but no evidence that it was released by field stimulation was obtained. Substance P had excitatory effects chiefly by release of acetylcholine. It, in addition to norepinephrine, at least in circular muscle, deserves evaluation as the mediator of noncholinergic excitation to high frequency field stimulation. Although vasoactive intestinal peptide sometimes had inhibitory effects, these were incomplete and inconsistent. However, further evaluation of its possible role as a nonadrenergic, noncholinergic inhibitory mediator is required to determine if it is involved as one component in the response. Few qualitative differences existed between responses of various regions of the colon to potential neuromediators, although there were some consistent differences between responses of longitudinal and circular muscle. Some differences existed in responses obtained earlier in vivo and in vitro. In particular, inhibitory effects following excitation by substance P on field stimulation were found only in vivo. Nonadrenergic, noncholinergic inhibitory responses to field stimulation were consistently present only in vitro. These differences have not been explained.


1993 ◽  
Vol 264 (6) ◽  
pp. E951-E957 ◽  
Author(s):  
C. B. Whorwood ◽  
P. C. Barber ◽  
J. Gregory ◽  
M. C. Sheppard ◽  
P. M. Stewart

In the rat kidney 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) maintains normal in vivo specificity for mineralocorticoid receptor (MR) by converting the active steroid corticosterone to inactive 11-dehydrocorticosterone, leaving aldosterone to occupy the MR. Clinical observations support the hypothesis that 11 beta-HSD also protects the distal colonic MR from glucocorticoid excess. We have measured 11 beta-HSD mRNA and activity along the rat colon and have analyzed the distribution of 11 beta-HSD, MR, and glucocorticoid receptor (GR) mRNA within rat distal colon using in situ hybridization. Levels of 11 beta-HSD mRNA (1.7 and 3.4 kb) and activity were higher in distal vs. proximal colon, paralleling reported MR mRNA levels. Within the distal colon mucosa both 11 beta-HSD immunoreactivity and mRNA was observed in cells in the lamina propria but not in epithelial cells. MR mRNA was present in surface epithelial cells, but was also colocalized with the same 11 beta-HSD-expressing cells in the lamina propria. In contrast GR mRNA was more uniformly distributed. The localization of MR mRNA to nonepithelial cells in the lamina propria, possibly neuroendocrine cells, suggests that mineralocorticoid-regulated sodium transport across colonic epithelial cells may also involve a paracrine mechanism. As with the kidney, exposure of active mineralocorticoid to the MR in these cells in the lamina propria is dictated by 11 beta-HSD in an autocrine fashion.


1991 ◽  
Vol 260 (4) ◽  
pp. G646-G652 ◽  
Author(s):  
M. Dapoigny ◽  
S. K. Sarna

We investigated the effect of physical exercise on colonic motor activity in the fasted and fed states in six conscious dogs. Each dog was implanted with nine strain gauge transducers: three on the proximal, three on the middle, and three on the distal colon. The dogs ran for 1 h on a treadmill at 5 km/h (slope 5%). In the fasted state, the dogs exercised during the 5th h of recording after an overnight fast, and in the fed state during the 1st, 3rd, and 5th postprandial hour. In the fasted state, exercise significantly decreased the frequency of colonic migrating motor complexes (MMCs) but had no effect on the total or the mean duration of contractile states in the proximal, middle, and distal colon. Postprandially, exercise disrupted colonic MMCs and replaced them with nonmigrating motor complexes in all three periods of exercise (1st, 3rd, and 6th h). Exercise also increased the total duration per hour of contractile activity throughout the colon during the 1st and 3rd h and only in the distal colon during the 6th h after the meal. The dogs never defecated during rest in the fasted or the fed state. Shortly after the start of exercise in the fasted and fed states, giant migrating contractions (GMCs) occurred, and they were followed by defecation. In approximately 40% of the experiments, another GMC originated in the proximal colon, approximately 10 min after the first defecation, and migrated caudad up to the middle colon. These GMCs were not associated with defecation but caused mass movements.(ABSTRACT TRUNCATED AT 250 WORDS)


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.


1989 ◽  
Vol 256 (6) ◽  
pp. G997-G1004 ◽  
Author(s):  
J. Y. Hou ◽  
M. F. Otterson ◽  
S. K. Sarna

We studied the effects of close intra-arterial injections of substance P on colonic motor activity in the conscious state, during anesthesia, and during acute laparotomy. In the conscious state, with enteric nerves intact, substance P stimulated postsynaptic cholinergic neurons to induce a large amplitude and long duration contraction. This response was blocked by prior close intra-arterial injection of atropine and tetrodotoxin (TTX) but not hexamethonium. Hexamethonium and TTX given alone, close intra-arterially, induced a series of short-duration contractions. Prior close intra-arterial administration of hexamethonium significantly enhanced the colonic motor response to substance P. After blockade of nerve conduction by TTX, substance P induced a series of short-duration contractions with characteristics different from those when the nerves were functioning. Anesthesia alone had little effect on the colonic motor response to substance P, but laparotomy inhibited it significantly. Laparotomy similarly inhibited the contractile response to bethanechol. Gut handling had no further effect on this inhibition. We conclude that in the conscious state substance P acts preferentially on postsynaptic cholinergic neurons to contract colonic circular muscle. When the intrinsic nerves are blocked, substance P may act directly on the smooth muscle to induce circular muscle contractions with characteristics different from those induced when nerves are intact. Substance P also has a weak inhibitory motor effect by its action on presynaptic neurons that synapse on postganglionic intrinsic inhibitory neurons. Anesthetic doses of barbiturates have no major effects on the neuromuscular response to substance P, but laparotomy significantly inhibits the smooth muscle response and selectively blocks some neurons.


2001 ◽  
Vol 280 (4) ◽  
pp. G546-G554 ◽  
Author(s):  
Asensio Gonzalez ◽  
Sushil K. Sarna

The aim of this study was to investigate the modulation of in vitro rat colonic circular muscle contractions by dextran sodium sulfate (DSS)-induced inflammation and in spontaneous inflammation in HLA-B27 rats. We also examined the potential role of hydrogen peroxide (H2O2) in modulating excitation-contraction coupling. The muscle strips from the middle colon generated spontaneous phasic contractions and giant contractions (GCs), the proximal colon strips generated primarily phasic contractions, and the distal colon strips were mostly quiescent. The spontaneous phasic contractions and GCs were not affected by inflammation, but the response to ACh was suppressed in DSS-treated rats and in HLA-B27 rats. H2O2production was increased in the muscularis of the inflamed colon. Incubation of colonic muscle strips with H2O2suppressed the spontaneous phasic contractions and concentration and time dependently reduced the response to ACh; in the middle colon, it also increased the frequency of GCs. We conclude that H2O2mimics the suppression of the contractile response to ACh in inflammation. H2O2also selectively suppresses phasic contractions and increases the frequency of GCs, as found previously in inflamed dog and human colons.


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