Restraint stress stimulates colonic motility via central corticotropin-releasing factor and peripheral 5-HT3 receptors in conscious rats

2007 ◽  
Vol 292 (4) ◽  
pp. G1037-G1044 ◽  
Author(s):  
Yukiomi Nakade ◽  
Hiroyuki Fukuda ◽  
Masahiro Iwa ◽  
Kiyoshi Tsukamoto ◽  
Hidenori Yanagi ◽  
...  
Keyword(s):  
Restraint Stress ◽  
Colonic Motility ◽  
Distal Colon ◽  
Proximal Colon ◽  
Colonic Transit ◽  
Corticotropin Releasing Factor ◽  
Entire Colon ◽  
Conscious Rats ◽  
Force Transducers ◽  
Intracisternal Injection

Although restraint stress accelerates colonic transit via a central corticotropin-releasing factor (CRF), the precise mechanism still remains unclear. We tested the hypothesis that restraint stress and central CRF stimulate colonic motility and transit via a vagal pathway and 5-HT3 receptors of the proximal colon in rats. 51Cr was injected via the catheter positioned in the proximal colon to measure colonic transit. The rats were subjected to a restraint stress for 90 min or received intracisternal injection of CRF. Ninety minutes after the administration of 51Cr, the entire colon was removed, and the geometric center (GC) was calculated. Four force transducers were sutured on the proximal, mid, and distal colon to record colonic motility. Restraint stress accelerated colonic transit (GC of 6.7 ± 0.4, n = 6) compared with nonrestraint controls (GC of 5.1 ± 0.2, n = 6). Intracisternal injection of CRF (1.0 μg) also accelerated colonic transit (GC of 7.0 ± 0.2, n = 6) compared with saline-injected group (GC of 4.6 ± 0.5, n = 6). Restraint stress-induced acceleration of colonic transit was reduced by perivagal capsaicin treatment. Intracisternal injection of CRF antagonists (10 μg astressin) abolished restraint stress-induced acceleration of colonic transit. Stimulated colonic transit and motility induced by restraint stress and CRF were significantly reduced by the intraluminal administration of 5-HT3 antagonist ondansetron (5 × 10−6 M; 1 ml) into the proximal colon. Restraint stress and intracisternal injection of CRF significantly increased the luminal content of 5-HT of the proximal colon. It is suggested that restraint stress stimulates colonic motility via central CRF and peripheral 5-HT3 receptors in conscious rats.

Electroacupuncture at ST-36 accelerates colonic motility and transit in freely moving conscious rats

2006 ◽  
Vol 290 (2) ◽  
pp. G285-G292 ◽  
Author(s):  
Masahiro Iwa ◽  
Megumi Matsushima ◽  
Yukiomi Nakade ◽  
Theodore N. Pappas ◽  
Mineko Fujimiya ◽  
...  
Keyword(s):  
Colonic Motility ◽  
Distal Colon ◽  
Proximal Colon ◽  
Colonic Transit ◽  
Motility Index ◽  
Conscious Rats ◽  
Beneficial Effects ◽  
Efferent Pathway ◽  
Bowel Diseases ◽  
Parasympathetic Pathway

Acupuncture is useful for functional bowel diseases, such as constipation and diarrhea. However, the mechanisms of beneficial effects of acupuncture on colonic function have scarcely ever been investigated. We tested the hypothesis that electroacupuncture (EA) at ST-36 stimulates colonic motility and transit via a parasympathetic pathway in conscious rats. Hook-shaped needles were inserted at bilateral ST-36 (lower limb) or BL-21 (back) and electrically stimulated at 10 Hz for 20 min. We also studied c-Fos expression in response to EA at ST-36 in Barrington's nucleus of the pons. EA at ST-36, but not BL-21, significantly increased the amplitude of motility at the distal colon. The calculated motility index of the distal colon increased to132 ± 9.9% of basal levels ( n = 14, P < 0.05). In contrast, EA at ST-36 had no stimulatory effects in the proximal colon. EA at ST-36 significantly accelerated colonic transit [geometric center (GC) = 6.76 ± 0.42, n = 9, P < 0.001] compared with EA at BL-21 (GC = 5.23 ± 0.39, n = 7). The stimulatory effect of EA at ST-36 on colonic motility and transit was abolished by pretreatment with atropine. EA-induced acceleration of colonic transit was also abolished by extrinsic nerve denervation of the distal colon (GC = 4.69 ± 0.33, n = 6). The number of c-Fos-immunopositive cells at Barrington's nucleus significantly increased in response to EA at ST-36 to 8.1 ± 1.1 cells/section compared with that of controls (2.4 ± 0.5 cells/section, n = 3, P < 0.01). It is concluded that EA at ST-36 stimulates distal colonic motility and accelerates colonic transit via a sacral parasympathetic efferent pathway (pelvic nerve). Barrington's nucleus plays an important role in mediating EA-induced distal colonic motility in conscious rats.

Luminally released serotonin stimulates colonic motility and accelerates colonic transit in rats

2007 ◽  
Vol 293 (1) ◽  
pp. R64-R69 ◽  
Author(s):  
Kiyoshi Tsukamoto ◽  
Hajime Ariga ◽  
Chris Mantyh ◽  
Theodore N. Pappas ◽  
Hidenori Yanagi ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Colonic Motility ◽  
Physiological Role ◽  
Distal Colon ◽  
Proximal Colon ◽  
Colonic Transit ◽  
Intraluminal Pressure ◽  
Ex Vivo Model ◽  
Colon Tissue ◽  
Ec Cells

Enterochromaffin (EC) cells of the epithelial cells release 5-HT into the lumen, as well as basolateral border. However, the physiological role of released 5-HT into the lumen is poorly understood. Concentrations of 5-HT in the colonic mucosa, colonic lumen, and feces were measured by HPLC in rats. To investigate whether intraluminal 5-HT accelerates colonic transit, 5-HT and 51Cr were administered into the lumen of the proximal colon, and colonic transit was measured. To investigate whether 5-HT is released into the lumen, we used an ex vivo model of isolated vascularly and luminally perfused rat proximal colon. To investigate whether luminal 5-HT is involved in regulating stress-induced colonic motility, the distal colonic motility was recorded under the stress loading, and a 5-HT3 receptor antagonist (ondansetron, 10−6 M, 0.5 ml) was administered intraluminally of the distal colon. Tissue content of 5-HT in the proximal colon (15.2 ± 4.3 ng/mg wet tissue) was significantly higher than that in the distal colon (3.3 ± 0.7 ng/mg wet tissue), while fecal content and luminal concentration of 5-HT was almost the same between the proximal and distal colon. Luminal administration of 5-HT (10−6–10−5 M) significantly accelerated colonic transit. Elevation of intraluminal pressure by 10 cmH2O significantly increased the luminal concentration of 5-HT but not the vascular concentration of 5-HT. Stress-induced stimulation of the distal colonic motility was significantly attenuated by the luminal administration of ondansetron. These results suggest that luminally released 5-HT from EC cells plays an important role in regulating colonic motility in rats.

Restraint stress augments postprandial gastric contractions but impairs antropyloric coordination in conscious rats

2006 ◽  
Vol 290 (3) ◽  
pp. R616-R624 ◽  
Author(s):  
Yukiomi Nakade ◽  
Daisuke Tsuchida ◽  
Hiroyuki Fukuda ◽  
Masahiro Iwa ◽  
Theodore N. Pappas ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Gastric Motility ◽  
Restraint Stress ◽  
Delayed Gastric Emptying ◽  
Corticotropin Releasing Factor ◽  
Conscious Rats ◽  
Cholinergic Pathway ◽  
Intracisternal Injection ◽  
Gastric Contractions

Central corticotropin-releasing factor (CRF) plays an important role in mediating restraint stress-induced delayed gastric emptying. However, it is unclear how restraint stress modulates gastric motility to delay gastric emptying. Inasmuch as solid gastric emptying is regulated via antropyloric coordination, we hypothesized that restraint stress impairs antropyloric coordination, resulting in delayed solid gastric emptying in conscious rats. Two strain gauge transducers were sutured onto the serosal surface of the antrum and pylorus, and postprandial gastric motility was monitored before, during, and after restraint stress. Antropyloric coordination, defined as a propagated single contraction from the antrum to the pylorus within 10 s, was followed by ≥20 s of quiescence. Restraint stress enhanced postprandial gastric motility in the antrum and pylorus to 140 ± 9% and 134 ± 9% of basal, respectively ( n = 6). The number of episodes of antropyloric coordination before restraint stress, 2.4 ± 0.4/10 min, was significantly reduced to 0.6 ± 0.3/10 min by restraint stress. Intracisternal injection of the CRF type 2 receptor antagonist astressin 2B (60 μg) or guanethidine partially restored restraint stress-induced impairment of antropyloric coordination (1.6 ± 0.3/10 min, n = 6). The restraint stress-induced augmentation of antral and pyloric contractions was increased by astressin 2B and guanethidine but abolished by atropine, hexamethonium, and vagotomy. Restraint stress enhanced postprandial gastric motility via a vagal cholinergic pathway. Restraint stress-induced delay of solid gastric emptying is due to impairment of antropyloric coordination. Restraint stress-induced impairment of antropyloric coordination might be mediated via a central CRF pathway.

Human urocortin II, a new CRF-related peptide, displays selective CRF2-mediated action on gastric transit in rats

2002 ◽  
Vol 282 (1) ◽  
pp. G34-G40 ◽  
Author(s):  
Mulugeta Million ◽  
Céline Maillot ◽  
Paul Saunders ◽  
Jean Rivier ◽  
Wylie Vale ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Intravenous Injection ◽  
Restraint Stress ◽  
Delayed Gastric Emptying ◽  
Colonic Transit ◽  
Corticotropin Releasing Factor ◽  
Solid Meal ◽  
Mediated Action ◽  
Conscious Rats ◽  
Stimulation Of

Human urocortin (hUcn) II is a new member of the corticotropin-releasing factor (CRF) family that selectively binds to the CRF2receptor. We investigated the CRF receptors involved in mediating the effects of hUcn II and human/rat CRF (h/rCRF) on gut transit. Gastric emptying, 4 h after a solid meal, and distal colonic transit (bead expulsion time) were monitored simultaneously in conscious rats. CRF antagonists were given subcutaneously 30 min before intravenous injection of peptides or partial restraint (for 90 min). hUcn II (3 or 10 μg/kg iv) inhibited gastric emptying (by 45% and 55%, respectively) and did not influence distal colonic transit. The CRF2 peptide antagonist astressin2-B blocked hUcn II action. h/rCRF, rat Ucn, and restraint delayed gastric emptying while accelerating distal colonic transit. The gastric response to intravenous h/rCRF and restraint was blocked by the CRF2 antagonist but not by the CRF1 antagonist CP-154,526, whereas the colonic response was blocked only by CP-154,526. None of the CRF antagonists influenced postprandial gut transit. These data show that intravenous h/rCRF and restraint stress-induced delayed gastric emptying involve CRF2 whereas stimulation of distal colonic transit involves CRF1. The distinct profile of hUcn II, only on gastric transit, is linked to its CRF2 selectivity.

Nitrergic regulation of colonic transit in rats

1999 ◽  
Vol 277 (2) ◽  
pp. G275-G279 ◽  
Author(s):  
Yohei Mizuta ◽  
Toku Takahashi ◽  
Chung Owyang
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Colonic Motility ◽  
Inhibitory Effect ◽  
Proximal Colon ◽  
Colonic Transit ◽  
Rat Colon ◽  
Inhibitory Neurotransmitter ◽  
Conscious Rats

Nitric oxide has been shown to be an inhibitory neurotransmitter in the mammalian colon, although its role in colonic transit remains unclear. We investigated the effect of the nitric oxide biosynthesis inhibitor NG -nitro-l-arginine methyl ester (l-NAME) on colonic transit in conscious rats. Colonic transit was determined by calculating the geometric center of the distribution of radiochromium instilled into the proximal colon. We also studied the effect ofl-NAME on colonic motility in vivo and on descending relaxation in vitro.l-NAME (10 mg/kg) significantly delayed colonic transit compared with saline. The inhibitory effect ofl-NAME was prevented byl-arginine (100 mg/kg) but not by d-arginine (100 mg/kg).l-NAME (10 mg/kg) induced random and uncoordinated phasic contractions throughout the rat colon in vivo. Luminal distension evoked descending relaxation in the proximal and distal rat colon in vitro.l-NAME (10−4 M) significantly inhibited this relaxation. It is suggested, therefore, that nitric oxide enhances transit in the rat colon by mediating descending relaxation, which, in turn, facilitates propulsion of the colonic contents.

Neurohumoral control of colonic motility in the rabbit

1983 ◽  
Vol 245 (4) ◽  
pp. G582-G588 ◽  
Author(s):  
W. J. Snape ◽  
S. Shiff
Keyword(s):  
Contractile Activity ◽  
Control Period ◽  
Colonic Motility ◽  
Distal Colon ◽  
Proximal Colon ◽  
Base Line ◽  
Cholinergic Stimulation ◽  
Bipolar Electrodes ◽  
Neurohumoral Control ◽  
Alpha Adrenergic Agonist

Colonic motility was examined in the proximal (taeniated) and distal (nontaeniated) colon of New Zealand White rabbits. Colonic myoelectric and contractile activities were recorded by bipolar electrodes and extraluminal strain gauges sewn on the antimesenteric serosal surface of the proximal and distal colon. Slow-wave frequency consistently was slower in the proximal colon (13.2 +/- 0.9) compared with the distal colon (15.8 +/- 1.2) (P less than 0.05). During the control period 81.8 +/- 5.2% of slow waves have superimposed spike potentials in the proximal colon. The distal colon had similar amounts of spike activity. The distal colon had increased base-line contractility (P less than 0.02). Atropine inhibited spike and contractile activity on both sides of the colon, but the distal colon still had more contractile activity than the proximal colon (P less than 0.02). The alpha-adrenergic agonist phenylephrine and antagonist phentolamine had no effect on colonic motility. Isoproterenol inhibited colonic smooth muscle spike and contractile activity. This effect was blocked by propranolol. Administration of trimethaphan camsylate caused an increase in spike and contractile activity only in the distal colon. The effect of trimethaphan on the distal colon was inhibited by atropine. These studies show that 1) tonic cholinergic stimulation exists both in the proximal and in the distal colon, 2) circulating catecholamines have minimal effect on base-line colonic motility, and 3) tonic nonadrenergic inhibition of the distal colon modulates the tonic cholinergic stimulation.

Butyrate enemas enhance both cholinergic and nitrergic phenotype of myenteric neurons and neuromuscular transmission in newborn rat colon

2012 ◽  
Vol 302 (12) ◽  
pp. G1373-G1380 ◽  
Author(s):  
Etienne Suply ◽  
Philine de Vries ◽  
Rodolphe Soret ◽  
François Cossais ◽  
Michel Neunlist
Keyword(s):  
Neuromuscular Transmission ◽  
Ex Vivo ◽  
Colonic Motility ◽  
Distal Colon ◽  
Postnatal Period ◽  
Colonic Transit ◽  
Rat Colon ◽  
Adult Rats ◽  
Myenteric Neurons

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.

scholarly journals Do corticotropin releasing factor-1 receptors influence colonic transit and bowel function in women with irritable bowel syndrome?

2009 ◽  
Vol 296 (6) ◽  
pp. G1299-G1306 ◽  
Author(s):  
Seth Sweetser ◽  
Michael Camilleri ◽  
Sara J. Linker Nord ◽  
Duane D. Burton ◽  
Lorna Castenada ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Colonic Motility ◽  
Bowel Function ◽  
Colonic Transit ◽  
Corticotropin Releasing Factor ◽  
Analysis Of Covariance ◽  
Eligibility Criteria ◽  
Double Blind ◽  
Safety Issues ◽  
Irritable Bowel

Corticotropin releasing factor (CRF), a mediator of stress response, alters gastrointestinal (GI) functions. Stress-related changes in colonic motility are blocked by selective CRF1 receptor antagonists. Our aim was to assess whether modulation of central and peripheral CRF1 receptors affects colonic transit and bowel function in female patients with diarrhea-predominant irritable bowel syndrome (D-IBS). This randomized, double-blind, placebo-controlled, 2-wk study evaluated the effects of oral pexacerfont (BMS-562086), a selective CRF1 receptor antagonist, 25 and 100 mg qd, on GI and colonic transit of solids [by validated scintigraphy with primary end point colonic geometric center (GC) at 24 h] and bowel function (by validated daily diaries) in 39 women with D-IBS. The 100-mg dose was comparable to a dose that inhibited colonic motility in stressed rats. Treatment effects were compared by analysis of covariance with baseline colonic transit as covariate. The study had 80% power (α = 0.05) to detect clinically meaningful (26%) differences in colonic transit. Thirty-nine of 55 patients fulfilled eligibility criteria (9 screen failures, 5 baseline GC24 outside prespecified range). At baseline, three treatment groups had comparable age, body mass index, and GC 24 h. Significant effects of pexacerfont relative to placebo were not detected on colonic GC24 ( P = 0.53), gastric emptying, orocecal transit, ascending colon emptying half-time, and stool frequency, consistency, and ease of passage. No safety issues were identified. We conclude that in women with D-IBS, pexacerfont, 25 or 100 mg qd, does not significantly alter colonic or other regional transit or bowel function. The role of central and peripheral CRF1 receptors in bowel function in D-IBS requires further study.

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