scholarly journals Peripheral peptide YY inhibits propulsive colonic motor function through Y2 receptor in conscious mice

2010 ◽  
Vol 298 (1) ◽  
pp. G45-G56 ◽  
Author(s):  
Lixin Wang ◽  
Guillaume Gourcerol ◽  
Pu-Qing Yuan ◽  
S. Vincent Wu ◽  
Mulugeta Million ◽  
...  
Keyword(s):  
Motor Function ◽  
Peptide Yy ◽  
Colonic Motility ◽  
Distal Colon ◽  
High Amplitude ◽  
Colonic Transit ◽  
Intraluminal Pressure ◽  
Antisecretory Effect ◽  
Nocturnal Feeding ◽  
Colonic Motor

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.

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.

5-Hydroxytryptophan activates colonic myenteric neurons and propulsive motor function through 5-HT4 receptors in conscious mice

2007 ◽  
Vol 292 (1) ◽  
pp. G419-G428 ◽  
Author(s):  
L. Wang ◽  
V. Martínez ◽  
H. Kimura ◽  
Y. Taché
Keyword(s):  
Motor Function ◽  
Colonic Motility ◽  
Distal Colon ◽  
Nadph Diaphorase ◽  
Maximal Response ◽  
Myenteric Neurons ◽  
Diaphorase Activity ◽  
Colonic Motor ◽  
Different Populations ◽  
Fos Expression

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.

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 ◽  
...  
Keyword(s):  
High Frequency ◽  
Colonic Motility ◽  
Distal Colon ◽  
High Amplitude ◽  
Corticotrophin Releasing Factor ◽  
Colonic Manometry ◽  
Colonic Motor ◽  
Chronic Stressors ◽  
Giant Migrating Contractions

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.

Urocortin I is present in the enteric nervous system and exerts an excitatory effect via cholinergic and serotonergic pathways in the rat colon

2007 ◽  
Vol 293 (4) ◽  
pp. G903-G910 ◽  
Author(s):  
Takazumi Kimura ◽  
Tomofumi Amano ◽  
Hirotsugu Uehara ◽  
Hajime Ariga ◽  
Tsuyoshi Ishida ◽  
...  
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Motor Function ◽  
Myenteric Plexus ◽  
Neuronal Cells ◽  
Colonic Transit ◽  
Rat Colon ◽  
Excitatory Effect ◽  
Potent Effect ◽  
Colonic Motor

Corticotropin-releasing factor (CRF) and urocortin I (UcnI) have been shown to accelerate colonic transit after central nervous system (CNS) or peripheral administration, but the mechanism of their peripheral effect on colonic motor function has not been fully investigated. Furthermore, the localization of UcnI in the enteric nervous system (ENS) of the colon is unknown. We investigated the effect of CRF and UcnI on colonic motor function and examined the localization of CRF, UcnI, CRF receptors, choline acetyltransferase (ChAT), and 5-HT. Isometric tension of rat colonic muscle strips was measured. The effect of CRF, UcnI on phasic contractions, and electrical field stimulation (EFS)-induced off-contractions were examined. The effects of UcnI on both types of contraction were also studied in the presence of antalarmin, astressin2-B, tetrodotoxin (TTX), atropine, and 5-HT antagonists. The localizations of CRF, UcnI, CRF receptors, ChAT, and 5-HT in the colon were investigated by immunohistochemistry. CRF and UcnI increased both contractions dose dependently. UcnI exerted a more potent effect than CRF. Antalarmin, TTX, atropine, and 5-HT antagonists abolished the contractile effects of UcnI. CRF and UcnI were observed in the neuronal cells of the myenteric plexus. UcnI and ChAT, as well as UcnI and 5-HT, were colocalized in some of the neuronal cells of the myenteric plexus. This study demonstrated that CRF and UcnI act on the ENS and increase colonic contractility by enhancing cholinergic and serotonergic neurotransmission. These peptides are present in myenteric neurons. CRF and, perhaps, to a greater extent, UcnI appear to act as neuromodulators in the ENS of the rat colon.

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.

Spinal modulation of duodenal and colonic motility and arterial pressure by neuropeptide Y, neuropeptide Y fragment 13–36, peptide YY, and pancreatic polypeptide in rats: involvement of the cholinergic nervous system

1993 ◽  
Vol 71 (2) ◽  
pp. 112-119 ◽  
Author(s):  
S. A. Wager-Pagé ◽  
E. Raizada ◽  
W. L. Veale ◽  
J. S. Davison
Keyword(s):  
Spinal Cord ◽  
Arterial Pressure ◽  
Neuropeptide Y ◽  
Pancreatic Polypeptide ◽  
Peptide Yy ◽  
Colonic Motility ◽  
Intraluminal Pressure ◽  
Thoracic Spinal Cord ◽  
Fold Family ◽  
Thoracic Spinal

The pancreatic polypeptide-fold (PP-fold) peptides, peptide YY (PYY) and pancreatic polypeptide (PP) (200 pmol), increased duodenal intraluminal pressure following intrathecal (IT) administration into the thoracic (T8–T10) spinal cord of urethane-anesthetized rats. Neuropeptide Y (NPY), PPY, and PP (IT) increased colonic intraluminal pressure of rats. The excitatory effects of the PP-fold peptides, NPY and PYY, were accompanied by increases in mean arterial pressure (MAP) during the same time period followed by a decrease to hypotensive levels. There were no further alterations of duodenal or colonic pressure in rats during the hypotensive period. The effect of PP (IT) on MAP was characterized by a pattern of hypotension frequently followed by a hypertensive period. The modulation of duodenal and colonic pressure does not differ between the members of the PP-fold family of peptides; however, the effects of the different members of the PP-fold family of peptides on MAP were varied. The Y2 receptor ligand, NPY (13–36) (200 pmol) (IT), did not alter duodenal and colonic pressure or MAP in rats. Therefore, the effects of PYY and NPY in the thoracic spinal cord on duodenal and colonic motility may be mediated via Y1 (postjunctional) receptors. Atropine, a muscarinic antagonist, attenuated NPY's (IT) excitatory effect on colonic pressure but did not alter the MAP response to this peptide. Atropine did not modify PYY's (IT) regulation of duodenal and colonic intraluminal pressure. However, atropine did attenuate PPY's inhibitory effect on MAP. The modulatory effects of PP (IT) on colonic pressure and MAP were attenuated by atropine, suggesting that the cholinergic system may be mediating the effects of this peptide. These observations provide further evidence that the modulation of gastrointestinal motility by PYY, PP, and NPY in the thoracic spinal cord is through different mechanisms.Key words: PP-fold peptides, duodenum, colon, atropine.

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.

scholarly journals Hydroxy-α sanshool induces colonic motor activity in rat proximal colon: a possible involvement of KCNK9

2015 ◽  
Vol 308 (7) ◽  
pp. G579-G590 ◽  
Author(s):  
Kunitsugu Kubota ◽  
Nobuhiro Ohtake ◽  
Katsuya Ohbuchi ◽  
Akihito Mase ◽  
Sachiko Imamura ◽  
...  
Keyword(s):  
Myenteric Plexus ◽  
Chinese Hamster Ovary Cells ◽  
Colonic Motility ◽  
Chinese Hamster ◽  
Intraluminal Pressure ◽  
Organ Bath ◽  
Long Distance ◽  
Healthy Humans ◽  
Colonic Motor ◽  
Defecation Frequency

Various colonic motor activities are thought to mediate propulsion and mixing/absorption of colonic content. The Japanese traditional medicine daikenchuto (TU-100), which is widely used for postoperative ileus in Japan, accelerates colonic emptying in healthy humans. Hydroxy-α sanshool (HAS), a readily absorbable active ingredient of TU-100 and a KCNK3/KCNK9/KCNK18 blocker as well as TRPV1/TRPA1 agonist, has been investigated for its effects on colonic motility. Motility was evaluated by intraluminal pressure and video imaging of rat proximal colons in an organ bath. Distribution of KCNKs was investigated by RT-PCR, in situ hybridization, and immunohistochemistry. Current and membrane potential were evaluated with use of recombinant KCNK3- or KCNK9-expressing Xenopus oocytes and Chinese hamster ovary cells. Defecation frequency in rats was measured. HAS dose dependently induced strong propulsive “squeezing” motility, presumably as long-distance contraction (LDC). TRPV1/TRPA1 agonists induced different motility patterns. The effect of HAS was unaltered by TRPV1/TRPA1 antagonists and desensitization. Lidocaine (a nonselective KCNK blocker) and hydroxy-β sanshool (a geometrical isomer of HAS and KCNK3 blocker) also induced colonic motility as a rhythmic propagating ripple (RPR) and a LDC-like motion, respectively. HAS-induced “LDC,” but not lidocaine-induced “RPR,” was abrogated by a neuroleptic agent tetrodotoxin. KCNK3 and KCNK9 were located mainly in longitudinal smooth muscle cells and in neural cells in the myenteric plexus, respectively. Administration of HAS or TU-100 increased defecation frequency in normal and laparotomy rats. HAS may evoke strong LDC possibly via blockage of the neural KCNK9 channel in the colonic myenteric plexus.

M1238 Peptide YY Acts Through Y2 Receptors to Inhibit Stimulated Colonic Motor Function in Conscious Mice

2008 ◽  
Vol 134 (4) ◽  
pp. A-367-A-368
Author(s):  
Lixin Wang ◽  
Guillaume Gourcerol ◽  
Pu-Qing Yuan ◽  
Mulugeta Million ◽  
Muriel H. Larauche ◽  
...  
Keyword(s):  
Motor Function ◽  
Peptide Yy ◽  
Colonic Motor

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.

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