Peripheral corticotropin-releasing factor (CRF) stimulates fos expression in the rat colonic myenteric neurons andfecal pellet output through CRF receptor subtype 1

2000 ◽  
Vol 118 (4) ◽  
pp. A638 ◽  
Author(s):  
Marcel Miampamba ◽  
Celine Maillot ◽  
Mulugeta Million ◽  
Yvette Tache
2018 ◽  
Vol 314 (5) ◽  
pp. G610-G622 ◽  
Author(s):  
Seiichi Yakabi ◽  
Lixin Wang ◽  
Hiroshi Karasawa ◽  
Pu-Qing Yuan ◽  
Kazuhiko Koike ◽  
...  

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.


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.


2011 ◽  
Vol 56 (No. 11) ◽  
pp. 551-560 ◽  
Author(s):  
A. Czujkowska ◽  
MB Arciszewski

&nbsp;Corticotropin releasing factor (CRF), a 41-amino acid neuropeptide widely distributed in the mammalian central nervous system, has been shown to influence several gastrointestinal functions. Recent studies show that CRF released locally from enteric nerves may also underlie alterations in gut function. In this study, immunohistochemisty was applied to demonstrate the presence of CRF in the jejunum of sheep. Using double immunohistochemical staining the co-localization of CRF with vasoactive intestinal peptide (VIP), galanin, tyrosine hydroxylase (TH), neuropeptide&nbsp;Y (NPY) and substance P (SP) was evaluated. The presence of CRF was detected in myenteric neurons (3.6 &plusmn; 0.9%) as well as in submucous neurons (10.5 &plusmn; 1.2%). In the ovine jejunum different numbers of CRF-expressing nerve fibres were detected in myenteric ganglia, submucous ganglia, circular smooth muscle layer, lamina muscularis mucosae and between mucosal glands. None of the CRF-positive enteric neurons and CRF-positive nerve fibres exhibited the presence of TH. CRF-immunoreactive (IR) myenteric neurons widely co-expressed VIP and/or NPY. A minor population of CRF-IR myenteric neurons additionally co-stored SP. Galanin was not present in CRF-IR myenteric neurons. The presence of VIP was observed in the vast majority of CRF-positive submucous neurons. Moderate numbers of CRF-IR sumbucous neurons co-expressing galanin or NPY were also found. The presence of SP in CRF-positive submucous neurons was noted only incidentally. In the circular smooth muscle layer CRF-IR/VIP-IR, CRF-IR/NPY-IR as well as CRF-IR/SP-IR nerve fibres were present. In the mucosal layer of the ovine jejunum CRF-IR nerve fibres co-stored additionally VIP, galanin, NPY or SP. This present study provides for the first time evidence that CRF present in different subclasses of enteric neurons may influence certain activities of the ovine jejunum. Co-localization studies indicate that VIP, galanin, SP and NPY functionally co-operate with CRF in the jejunum of the sheep. &nbsp;


1995 ◽  
Vol 92 (3) ◽  
pp. 836-840 ◽  
Author(s):  
T. W. Lovenberg ◽  
C. W. Liaw ◽  
D. E. Grigoriadis ◽  
W. Clevenger ◽  
D. T. Chalmers ◽  
...  

2017 ◽  
Vol 102 (6) ◽  
pp. 1299-1312 ◽  
Author(s):  
Saravanan Ayyadurai ◽  
Amelia J. Gibson ◽  
Susan D’Costa ◽  
Elizabeth L. Overman ◽  
Laura J. Sommerville ◽  
...  

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