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 VIP is involved in peripheral CRF-induced stimulation of propulsive colonic motor function and diarrhea in male rats

2018 ◽  
Vol 314 (5) ◽  
pp. G610-G622 ◽  
Author(s):  
Seiichi Yakabi ◽  
Lixin Wang ◽  
Hiroshi Karasawa ◽  
Pu-Qing Yuan ◽  
Kazuhiko Koike ◽  
...  
Keyword(s):  
Vasoactive Intestinal Peptide ◽  
Motor Function ◽  
Terminal Ileum ◽  
Proximal Colon ◽  
Corticotropin Releasing Factor ◽  
Submucosal Plexus ◽  
Myenteric Neurons ◽  
Colonic Motor ◽  
Fos Expression ◽  
Stimulation Of

We investigated whether vasoactive intestinal peptide (VIP) and/or prostaglandins contribute to peripheral corticotropin-releasing factor (CRF)-induced CRF1 receptor-mediated stimulation of colonic motor function and diarrhea in rats. The VIP antagonist, [4Cl-D-Phe6, Leu17]VIP injected intraperitoneally completely prevented CRF (10 µg/kg ip)-induced fecal output and diarrhea occurring within the first hour after injection, whereas pretreatment with the prostaglandins synthesis inhibitor, indomethacin, had no effect. In submucosal plexus neurons, CRF induced significant c-Fos expression most prominently in the terminal ileum compared with duodenum and jejunum, whereas no c-Fos was observed in the proximal colon. c-Fos expression in ileal submucosa was colocalized in 93.4% of VIP-positive neurons and 31.1% of non-VIP-labeled neurons. CRF1 receptor immunoreactivity was found on the VIP neurons. In myenteric neurons, CRF induced only a few c-Fos-positive neurons in the ileum and a robust expression in the proximal colon (17.5 ± 2.4 vs. 0.4 ± 0.3 cells/ganglion in vehicle). The VIP antagonist prevented intraperitoneal CRF-induced c-Fos induction in the ileal submucosal plexus and proximal colon myenteric plexus. At 60 min after injection, CRF decreased VIP levels in the terminal ileum compared with saline (0.8 ± 0.3 vs. 2.5 ± 0.7 ng/g), whereas VIP mRNA level detected by qPCR was not changed. These data indicate that intraperitoneal CRF activates intestinal submucosal VIP neurons most prominently in the ileum and myenteric neurons in the colon. It also implicates VIP signaling as part of underlying mechanisms driving the acute colonic secretomotor response to a peripheral injection of CRF, whereas prostaglandins do not play a role. NEW & NOTEWORTHY Corticotropin-releasing factor (CRF) in the gut plays a physiological role in the stimulation of lower gut secretomotor function induced by stress. We showed that vasoactive intestinal peptide (VIP)-immunoreactive neurons in the ileal submucosal plexus expressed CRF1 receptor and were prominently activated by CRF, unlike colonic submucosal neurons. VIP antagonist abrogated CRF-induced ileal submucosal and colonic myenteric activation along with functional responses (defecation and diarrhea). These data point to VIP signaling in ileum and colon as downstream effectors of CRF.

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.

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.

Monosynaptic reflexes, c-fos expression, and NADPH-diaphorase activity in the cat spinal cord: Changes induced by chronic muscle inflammation

2007 ◽  
Vol 39 (3) ◽  
pp. 191-200 ◽  
Author(s):  
H. Steffens ◽  
E. D. Schomburg ◽  
A. V. Maznychenko ◽  
V. A. Maisky ◽  
A. I. Kostyukov ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Nadph Diaphorase ◽  
Muscle Inflammation ◽  
Diaphorase Activity ◽  
Fos Expression

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.

scholarly journals Nitric Oxide Regulates Estrus Cycle Dependent Colonic Motility in Mice

2021 ◽  
Vol 15 ◽  
Author(s):  
Gayathri K. Balasuriya ◽  
Saseema S. Nugapitiya ◽  
Elisa L. Hill-Yardin ◽  
Joel C. Bornstein
Keyword(s):  
Nitric Oxide ◽  
Estrogen Receptor Alpha ◽  
Ex Vivo ◽  
Colonic Motility ◽  
Inhibitory Neurotransmitter ◽  
Myenteric Neurons ◽  
Female Mice ◽  
Colonic Motor ◽  
Bowel Disorders ◽  
Cycle Dependent

Women are more susceptible to functional bowel disorders than men and the severity of their symptoms such as diarrhea, constipation, abdominal pain and bloating changes over the menstrual cycle, suggesting a role for sex hormones in gastrointestinal function. Nitric oxide (NO) is a major inhibitory neurotransmitter in the gut and blockade of nitric oxide synthase (NOS; responsible for NO synthesis) increases colonic motility in male mice ex vivo. We assessed the effects of NOS inhibition on colonic motility in female mice using video imaging analysis of colonic motor complexes (CMCs). To understand interactions between NO and estrogen in the gut, we also quantified neuronal NOS and estrogen receptor alpha (ERα)-expressing myenteric neurons in estrus and proestrus female mice using immunofluorescence. Mice in estrus had fewer CMCs under control conditions (6 ± 1 per 15 min, n = 22) compared to proestrus (8 ± 1 per 15 min, n = 22, One-way ANOVA, p = 0.041). During proestrus, the NOS antagonist N-nitro-L-arginine (NOLA) increased CMC numbers compared to controls (189 ± 46%). In contrast, NOLA had no significant effect on CMC numbers during estrus. During estrus, we observed more NOS-expressing myenteric neurons (48 ± 2%) than during proestrus (39 ± 1%, n = 3, p = 0.035). Increased nuclear expression of ERα was observed in estrus which coincided with an altered motility response to NOLA in contrast with proestrus when ERα was largely cytoplasmic. In conclusion, we confirm a cyclic and sexually dimorphic effect of NOS activity in female mouse colon, which could be due to genomic effects of estrogens via ERα.

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