Serotonin and vasoactive intestinal peptide antagonists attenuate rotavirus diarrhoea

Kordasti, Shirin; Sjövall, Henrik; Lundgren, Ove; Svensson, Lennart

doi:10.1136/gut.2003.033563

Cited by 79 publications

(62 citation statements)

References 43 publications

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“…shown that drugs that inhibit the function of the ENS also could reduce symptoms of rotavirus disease in mice 75,76 .…”

Section: Results and Discussion Of The Papersmentioning

confidence: 99%

“…VIP, 5--HT) and increase motility (e.g. 5--HT), rotavirus diarrhea was attenuated in mice pups 75 . Moreover, loperamide a drug acting on myenteric neurons, and atropine, acting on muscarinic acetylcholine receptors on nerves and enteric muscle cells, both attenuated diarrhea of infant mice 99 , further supporting the role of ENS in rotavirus diarrhea.…”

Section: The Enteric Nervous Systemmentioning

confidence: 99%

“…The myenteric plexus provides motor innervation to the circular muscle layer and the longitudinal muscle and regulates intestinal motility including peristalsis 142 . Over the years, it has become more and more evident that ENS is involved in rotavirus diarrhea 30,[74][75][76][77] . By blocking enteric neurotransmitters, that can act to induce active secretion (e.g.…”

Section: The Enteric Nervous Systemmentioning

confidence: 99%

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Rotavirus Disease Mechanisms Diarrhea, Vomiting and Inflammation : How and Why

Hagbom¹

2015

Linköping University Medical Dissertations

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Rotavirus infections cause diarrhea and vomiting that can lead to severe dehydration. Despite extensive tissue damage and cell death, the inflammatory response is very limited. The focus of this thesis was to study pathophysiological mechanisms behind diarrhea and vomiting during rotavirus infection and also to investigate the mechanism behind the limited inflammatory response. An important discovery in this thesis was that rotavirus infection and the rotavirus toxin NSP4 stimulate release of the neurotransmitter serotonin from intestinal sensory enterochromaffin cells, in vitro and ex vivo. Interestingly, serotonin is known to be a mediator of both diarrhea and vomiting. Moreover, mice pups infected with rotavirus responded with central nervous system (CNS) activation in brain structures associated with vomiting, thus indicating a cross-talk between the gut and brain in rotavirus disease. Our finding that rotavirus infection activates the CNS led us to address the hypothesis that rotavirus infection not only activates the vagus nerve to stimulate vomiting, but also suppresses the inflammatory response via the cholinergic anti-inflammatory pathway, both of which are mediated by activated vagal afferent nerve signals into the brain stem. We found that mice lacking an intact vagus nerve, and mice lacking the α7 nicotine acetylcholine receptor (nAChR), being involved in cytokine suppression from macrophages, responded with a higher inflammatory response. Moreover, stimulated cytokine release from macrophages, by the rotavirus toxin NSP4, could be attenuated by nicotine, an agonist of the α7 nAChR. Thus, it seems most reasonable that the cholinergic anti-inflammatory pathway contributes to the limited inflammatory response during rotavirus infection. Moreover, rotavirus-infected mice displayed increased intestinal motility at the onset of diarrhea, which was not associated with increased intestinal permeability. The increased motility and diarrhea in infant mice could be attenuated by drugs acting on the enteric nervous system, indicating the importance and contribution of nerves in the rotavirus mediated disease. In conclusion, this thesis provides further insight into the pathophysiology of diarrhea and describe for the first time how rotavirus and host cross-talk to induce the vomiting reflex and limit inflammation. Results from these studies strongly support our hypothesis that serotonin and activation of the enteric nervous system and CNS contributes to diarrhea, vomiting and suppression of the inflammatory response in rotavirus disease

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“…shown that drugs that inhibit the function of the ENS also could reduce symptoms of rotavirus disease in mice 75,76 .…”

Section: Results and Discussion Of The Papersmentioning

confidence: 99%

Section: The Enteric Nervous Systemmentioning

confidence: 99%

Section: The Enteric Nervous Systemmentioning

confidence: 99%

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Rotavirus Disease Mechanisms Diarrhea, Vomiting and Inflammation : How and Why

Hagbom¹

2015

Linköping University Medical Dissertations

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“…In a phase III trial, NK2 receptor antagonists reduced NKA-induced gut motility in healthy volunteers, but not the NKA-induced flush (49) that is probably mediated by NK1 receptors (50). Others have shown that SP receptor antagonists shortened the duration of diarrhea in mice (51).…”

Section: Discussionmentioning

confidence: 99%

Tachykinins in endocrine tumors and the carcinoid syndrome

Cunningham¹,

Janson²,

Agarwal³

et al. 2008

European Journal of Endocrinology

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Objective: A new antibody, active against the common tachykinin (TK) C-terminal, was used to study TK expression in patients with endocrine tumors and a possible association between plasma-TK levels and symptoms of diarrhea and flush in patients with metastasizing ileocecal serotonin-producing carcinoid tumors (MSPCs). Method: TK, serotonin and chromogranin A (CgA) immunoreactivity (IR) was studied by immunohistochemistry in tissue samples from 33 midgut carcinoids and 72 other endocrine tumors. Circulating TK (P-TK) and urinary-5 hydroxyindoleacetic acid (U-5HIAA) concentrations were measured in 42 patients with MSPCs before treatment and related to symptoms in patients with the carcinoid syndrome. Circulating CgA concentrations were also measured in 39 out of the 42 patients. Results: All MSPCs displayed serotonin and strong TK expression. TK-IR was also seen in all serotoninproducing lung and appendix carcinoids. None of the other tumors examined contained TK-IR cells. Concentrations of P-TK, P-CgA, and U-5HIAA were elevated in patients experiencing daily episodes of either flush or diarrhea, when compared with patients experiencing occasional or none of these symptoms. In a Spearman partial rank test, the correlation of P-TK with daily diarrhea was independent of both U-5HIAA and CgA levels. Conclusion: We found that TK synthesis occurs in serotonin-IR tumors and that P-TK levels are significantly correlated with symptoms of flush and diarrhea in patients with MSPCs. This is, to our knowledge, the first report demonstrating an independent correlation of P-TKs with carcinoid diarrhea, a symptom that is customarily regarded as serotonin mediated. Further investigations may present opportunities for new therapeutic possibilities.European Journal of Endocrinology 159 275-282

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“…The gastrointestinal tract provides the main route of access to the host for several viruses (Oberste et al 2000), including the human immunodeficiency virus (Smith et al 2003) and poliovirus (Mueller et al 2005), and for unconventional viruses or agents such as those involved in prion diseases (McBride et al 2001). These viruses can cause gastroenteritis, which is characterized by electrolyte and fluid secretion that seems to be triggered by local neural reflexes whose mechanism of activation is at present unknown (Morris and Estes 2001;Kordasti et al 2004). Some enteroviruses also show different degrees of neurotropism and neurovirulence that can lead to overt cytotoxic effects, latent infection, or viral spreading to the CNS (Irie et al 1989;Morrison et al 1991;Chen et al 2003;Holland-Cunz et al 2006;Selgrad et al 2009).…”

Section: Discussionmentioning

confidence: 99%

Toll-like Receptors 3, 4, and 7 Are Expressed in the Enteric Nervous System and Dorsal Root Ganglia

Barajon¹,

Serrao

Arnaboldi

et al. 2009

J Histochem Cytochem.

250

199

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S U M M A R Y The aim of the present study was to evaluate the expression of innate immunity receptors belonging to the Toll-like family in the neural plexuses of the different tracts of murine intestine, of the human ileum, and in lower dorsal root ganglia (DRGs) from where extrinsic afferents to these plexuses originate. Results obtained by immunohistochemistry and immunofluorescence on paraffin-embedded tissue and whole-mount preparations show that Toll-like receptors (TLRs) -3 and -7, recognizing viral RNA, and TLR4, recognizing lipopolysaccharide (membrane component of Gram-negative bacteria), are expressed in the myenteric and submucous plexuses of murine intestine and human ileum, and in DRGs primary sensory neurons. They also show that TLR4 immunostaining is stronger in murine distal large bowel. In murine tissue, expression of TLRs was present in both neurons and glial cells. These observations indicate that the enteric neural network might be directly activated by bacterial and viral components and is therefore more in the forefront than previously envisaged in defense responses of the intestinal wall and in the cross-talk with intestinal microbiota. They also highlight the presence of a peripheral neural network that by way of hardwired neurotransmission could potentially convey to the central nervous system specific information on our microbial counterpart and invading or potentially invading pathogens. (J Histochem Cytochem

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Serotonin and vasoactive intestinal peptide antagonists attenuate rotavirus diarrhoea

Cited by 79 publications

References 43 publications

Rotavirus Disease Mechanisms Diarrhea, Vomiting and Inflammation : How and Why

Rotavirus Disease Mechanisms Diarrhea, Vomiting and Inflammation : How and Why

Tachykinins in endocrine tumors and the carcinoid syndrome

Toll-like Receptors 3, 4, and 7 Are Expressed in the Enteric Nervous System and Dorsal Root Ganglia

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