Prostaglandin E2 activation of VIP secretomotor neurons in the guinea pig ileum

Dekkers, J.A.J.M.; Kroese, A.B.A.; Keenan, Catherine M.; MacNaughton, Wallace K.; Sharkey, Keith A.

doi:10.1016/s0165-1838(97)00079-9

Cited by 25 publications

(17 citation statements)

References 18 publications

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“…It is possible that the persistence of pCREB activation in response to distension occurred because the ENS contains neurons in which the action potential current is carried in part by Ca 2ϩ and is thus TTX-resistant (see Wood, 1994). Alternatively, it may have been mediated by a direct effect on epithelial cells (Dekkers et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Differential localization of Ca2+ channel ?1 subunits in the enteric nervous system: Presence of ?1B channel-like immunoreactivity in intrinsic primary afferent neurons

Kirchgessner

Liu

1999

J. Comp. Neurol.

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Section: Discussionmentioning

confidence: 99%

Differential localization of Ca2+ channel ?1 subunits in the enteric nervous system: Presence of ?1B channel-like immunoreactivity in intrinsic primary afferent neurons

Kirchgessner

Liu

1999

J. Comp. Neurol.

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“…Having shown that VIP seemed to mediate the anti-inflammatory effects of GLP-2, we next investigated whether neurons that release VIP were activated by GLP-2. We assessed neuronal activation by using cFos, as previously described (8,34). In these studies, the numbers of activated neurons within the enteric nervous system and the numbers expressing VIP were quantified by immunohistochemical staining by using naïve animals following injection with GLP-2 sc or control vehicle (Fig.…”

Section: Effects Of Glp-2 On Intestinal Inflammationmentioning

confidence: 99%

Enteric neural pathways mediate the anti-inflammatory actions of glucagon-like peptide 2

Sigalet¹,

Wallace²,

Holst³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

159

149

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is an important regulator of nutritional absorptive capacity with antiinflammatory actions. We hypothesized that GLP-2 reduces intestinal mucosal inflammation by activation of vasoactive intestinal polypeptide (VIP) neurons of the submucosal plexus. Ileitis or colitis was induced in rats by injection of trinitrobenzene sulfonic acid (TNBS), or colitis was induced by administration of dextran sodium sulfate (DSS) in drinking water. Subsets of animals received (1-33)-GLP-2 (50 g/kg sc bid) either immediately or 2 days after the establishment of inflammation and were followed for 3-5 days. The involvement of VIP neurons was assessed by concomitant administration of GLP-2 and the VIP antagonist [Lys 1 -Pro 2,5 -Arg 3,4 -Tyr 6 ]VIP and by immunohistochemical labeling of GLP-2-activated neurons. In all models, GLP-2 treatment, whether given immediately or delayed until inflammation was established, resulted in significant improvements in animal weights, mucosal inflammation indices (myeloperoxidase levels, histological mucosal scores), and reduced levels of inflammatory cytokines (IFN-␥, TNF-␣, IL-1␤) and inducible nitric oxide synthase, with increased levels of IL-10 in TNBS ileitis and DSS colitis. Reduced rates of crypt cell proliferation and of apoptosis within crypts in inflamed tissues were also noted with GLP-2 treatment. These effects were abolished with coadministration of GLP-2 and the VIP antagonist. GLP-2 was shown to activate neurons and to increase the number of cells expressing VIP in the submucosal plexus of the ileum. These findings suggest that GLP-2 acts as an anti-inflammatory agent through activation of enteric VIP neurons, independent of proliferative effects. They support further studies to examine the role of neural signaling in the regulation of intestinal inflammation. vasoactive intestinal peptide; trinitrobenzene sulfonic acid colitis; dextran sodium sulfate colitis; Crohn's disease THE ENTEROENDOCRINE HORMONE glucagon-like peptide-2 (GLP-2) is thought to act primarily as a regulator of intestinal nutrient absorption and as an intestinal-specific trophic factor (10, 12, 26). As a trophic factor, GLP-2 stimulates crypt cell proliferation, nutrient transporter expression, and intestinal blood flow (27) through actions on a specific receptor system primarily localized to enteric neurons and enteroendocrine cells (4,20,35). In studies using dextran sodium sulfate (DSS) and indomethacin models of intestinal inflammation, GLP-2 stimulation has been shown to improve mucosal healing (6, 13, 24); mechanistically, this was ascribed to an increased crypt cell proliferation rate (13).Given the evidence that GLP-2 receptors appear to be localized to the enteric nervous system, we speculated that GLP-2 may induce anti-inflammatory effects via this pathway. Specifically, vasoactive intestinal polypeptide (VIP) has been shown to act as an anti-inflammatory agent (2), and so we hypothesized that GLP-2 may act by stimulating neuronal VIP release in the intestinal submucosa and mucosa. Subsequently, it has bee...

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“…C, D: VIP immunoreactive neurons (C, arrow) of the submucosal plexus express Fos (D, arrow) in response to application of PGE 2 (100nM). See Dekkers et al, 1997b for details. E, F: VIP immunoreactive neurons (green) of the submucosal plexus of the ileum (E) and colon (F), express Fos (red) in response to application of IL-1␤ (10ng/ml).…”

Section: Enteric Innervation In Inflammationanimal Studiesmentioning

confidence: 99%

“…A more selective activation of enteric neurons (with presumably long-term effects on their function) has been observed by measurement of Fos expression in response to PGE 2 application (Dekkers et al, 1997b). Incubation of guinea-pig ileum with 10-1000 nM PGE 2 for 30 min caused a concentration-dependent increase in Fos immunoreactivity in submucosal neurons but curiously not in myenteric neurons.…”

Section: Enteric Neurons As Targets For Immune Mediatorsmentioning

confidence: 99%

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Consequences of intestinal inflammation on the enteric nervous system: Neuronal activation induced by inflammatory mediators

2001

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Prostaglandin E2 activation of VIP secretomotor neurons in the guinea pig ileum

Cited by 25 publications

References 18 publications

Differential localization of Ca2+ channel ?1 subunits in the enteric nervous system: Presence of ?1B channel-like immunoreactivity in intrinsic primary afferent neurons

Differential localization of Ca2+ channel ?1 subunits in the enteric nervous system: Presence of ?1B channel-like immunoreactivity in intrinsic primary afferent neurons

Enteric neural pathways mediate the anti-inflammatory actions of glucagon-like peptide 2

Consequences of intestinal inflammation on the enteric nervous system: Neuronal activation induced by inflammatory mediators

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