| 1. |
- Hagbom, Marie, et al.
(författare)
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Rotavirus Stimulates Release of Serotonin (5-HT) from Human Enterochromaffin Cells and Activates Brain Structures Involved in Nausea and Vomiting
- 2011
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Ingår i: PLOS PATHOGENS. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 7:7
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Tidskriftsartikel (refereegranskat)abstract
- otavirus (RV) is the major cause of severe gastroenteritis in young children. A virus-encoded enterotoxin, NSP4 is proposed to play a major role in causing RV diarrhoea but how RV can induce emesis, a hallmark of the illness, remains unresolved. In this study we have addressed the hypothesis that RV-induced secretion of serotonin (5-hydroxytryptamine, 5-HT) by enterochromaffin (EC) cells plays a key role in the emetic reflex during RV infection resulting in activation of vagal afferent nerves connected to nucleus of the solitary tract (NTS) and area postrema in the brain stem, structures associated with nausea and vomiting. Our experiments revealed that RV can infect and replicate in human EC tumor cells ex vivo and in vitro and are localized to both EC cells and infected enterocytes in the close vicinity of EC cells in the jejunum of infected mice. Purified NSP4, but not purified virus particles, evoked release of 5-HT within 60 minutes and increased the intracellular Ca(2+) concentration in a human midgut carcinoid EC cell line (GOT1) and ex vivo in human primary carcinoid EC cells concomitant with the release of 5-HT. Furthermore, NSP4 stimulated a modest production of inositol 1,4,5-triphosphate (IP(3)), but not of cAMP. RV infection in mice induced Fos expression in the NTS, as seen in animals which vomit after administration of chemotherapeutic drugs. The demonstration that RV can stimulate EC cells leads us to propose that RV disease includes participation of 5-HT, EC cells, the enteric nervous system and activation of vagal afferent nerves to brain structures associated with nausea and vomiting. This hypothesis is supported by treating vomiting in children with acute gastroenteritis with 5-HT(3) receptor antagonists.
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| 2. |
- Hagbom, Marie, et al.
(författare)
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Towards a human rotavirus disease model
- 2012
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Ingår i: Current Opinion in Virology. - : Elsevier BV. - 1879-6257. ; 2:4, s. 408-418
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Tidskriftsartikel (refereegranskat)abstract
- While the clinical importance of human rotavirus (RV) disease is well recognized and potent vaccines have been developed, our understanding of how human RV causes diarrhoea, vomiting and death remains unresolved. The fact that oral rehydration corrects electrolyte and water loss, indicates that enterocytes in the small intestine have a functional sodium-glucose co-transporter. Moreover, RV infection delays gastric emptying and loperamide appears to attenuate RV diarrhoea, thereby suggesting activation of the enteric nervous system. Serotonin (5-HT) receptor antagonists attenuate vomiting in young children with gastroenteritis while zinc and enkephalinase inhibitors attenuate RV-induced diarrhoea. In this review we discuss clinical symptoms, pathology, histology and treatment practices for human RV infections and compile the data into a simplified disease model.
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| 3. |
- Jonsdottir, Ingibjörg H, 1966, et al.
(författare)
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Somatic nerve stimulation and cholera-induced net fluid secretion in the small intestine of the rat: evidence for an opioid effect.
- 1999
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Ingår i: Journal of the autonomic nervous system. - 0165-1838. ; 78:1, s. 18-23
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Tidskriftsartikel (refereegranskat)abstract
- The effects of somatic nerve stimulation on cholera toxin induced secretion was investigated in vivo in anaesthetised rats. Small intestinal secretion was induced with cholera toxin and measured by a gravimetric technique. Afferent stimulation (pulse frequency within train; 100 Hz; train duration: 50 ms; train frequency: 3 Hz) of the sciatic nerve over 30 min significantly reduced the net fluid secretion both during (P < 0.05) and after cessation of the stimulation (P < 0.01). The greatest effect was obtained immediately after the termination of the nerve stimulation when the secretion was reversed to net fluid absorption. The opioid receptor antagonist naloxone (10 mg kg(-1) i.v.) administrated during the stimulation, significantly inhibited the antisecretory effect seen after the stimulation, thus no significant difference was seen between the control period and the periods after cessation of the stimulation. The opioid receptor antagonist naloxone methiodide (10 mg kg(-1) i.v.), which does not cross the blood-brain barrier, partly inhibited the antisecretory effects but not with the same magnitude as naloxone, thus the net fluid secretion was still significantly inhibited after the stimulation (P < 0.05). We conclude that afferent stimulation of the sciatic nerve strongly inhibits the cholera toxin induced secretion in the small intestine. This inhibition involves primarily a central opioid mechanism and to a lesser extent peripheral opioid mechanism.
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| 4. |
- Kordasti, Shirin, 1975, et al.
(författare)
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Rotavirus infection is not associated with small intestinal fluid secretion in the adult mouse.
- 2006
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Ingår i: Journal of virology. - 0022-538X .- 1098-5514. ; 80:22, s. 11355-61
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Tidskriftsartikel (refereegranskat)abstract
- In contrast to humans, adult but not infant small animals are resistant to rotavirus diarrhea. The pathophysiological mechanism behind this age-restricted diarrhea is currently unresolved, and this question was investigated by studying the secretory state of the small intestines of adult mice infected with rotavirus. Immunohistochemistry and histological examinations revealed that rotavirus (strain EDIM) infects all parts of the small intestines of adult mice, with significant numbers of infected cells in the ilea at 2 and 4 days postinfection. Furthermore, quantitative PCR revealed that 100-fold more viral RNA was produced in the ilea than in the jejuna or duodena of adult mice. In vitro perfusion experiments of the small intestine did not reveal any significant changes in net fluid secretion among mice infected for 3 days or 4 days or in those that were noninfected (37 +/- 9 microl . h(-1) . cm(-1), 22 +/- 13 microl . h(-1) . cm(-1), and 33 +/- 6 microl . h(-1) . cm(-1), respectively) or in transmucosal potential difference (4.0 +/- 0.3 mV versus 3.9 +/- 0.4 mV), a marker for active chloride secretion, between control and rotavirus-infected mice. In vivo experiments also did not show any differences in potential difference between uninfected and infected small intestines. Furthermore, no significant differences in weight between infected and uninfected small intestines were found, nor were any differences in fecal output observed between infected and control mice. Altogether, these data suggest that rotavirus infection is not sufficient to stimulate chloride and water secretion from the small intestines of adult mice.
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| 5. |
- Kordasti, Shirin, 1975, et al.
(författare)
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Serotonin and vasoactive intestinal peptide antagonists attenuate rotavirus diarrhoea.
- 2004
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 53:7, s. 952-7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: The mechanisms underlying intestinal secretion in rotavirus diarrhoea remain to be established. We previously reported that rotavirus evokes intestinal fluid and electrolyte secretion by activation of the enteric nervous system. We now report that antagonists for the 5-hydroxytryptamine 3 receptor (5-HT(3)) and vasoactive intestinal peptide (VIP) receptor, but not antagonists for 5-hydroxytryptamine 4 receptor or the muscarinic receptor, attenuate rotavirus induced diarrhoea. METHODS: Neurotransmitter antagonists were administered to wild-type or neurokinin 1 receptor knockout mice infected with homologous (EDIM) or heterologous (RRV) rotavirus. RESULTS: While RRV infected mice had diarrhoea for 3.3 (0.2) days (95% confidence interval (CI) 3.04-3.56), the 5-HT(3) receptor antagonist (granisetron) and the VIP receptor antagonist (4Cl-D-Phe(6),Leu(17))-VIP both reduced the total number of days of RRV induced diarrhoea to 2.1 (0.3) (95% CI 1.31-2.9) (p<0.01). EDIM infected mice treated with granisetron had a significantly shorter duration of diarrhoea (5.6 (0.4) days) compared with untreated mice (8.0 (0.4) days; p<0.01). Experiments with neurokinin 1 receptor antagonists suggest that this receptor may possibly be involved in the secretory response to rotavirus. On the other hand, rotavirus diarrhoea was not attenuated in the neurokinin 1 receptor knockout mice. CONCLUSIONS: Our results suggest that the neurotransmitters serotonin and VIP are involved in rotavirus diarrhoea; observations that could imply new principles for treatment of this disease with significant global impact.
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| 6. |
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| 7. |
- Lundgren, Ove, 1937
(författare)
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Interface between the intestinal environment and the nervous system.
- 2004
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Ingår i: Gut. - 0017-5749. ; 53 Suppl 2
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Tidskriftsartikel (refereegranskat)abstract
- Possible mechanisms by which the intestinal contents may influence afferent nerve fibres in the lamina propria of the intestinal mucosa are discussed in this brief review. After addressing intestinal epithelial permeability, endocrine and brush cells are discussed, as well as enterocytes, as sensors for luminal microbes.
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| 8. |
- Lundgren, Ove, 1937, et al.
(författare)
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Intestinal Epithelial Stem/Progenitor Cells Are Controlled by Mucosal Afferent Nerves
- 2011
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:2, s. 16295-
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Tidskriftsartikel (refereegranskat)abstract
- Background: The maintenance of the intestinal epithelium is of great importance for the survival of the organism. A possible nervous control of epithelial cell renewal was studied in rats and mice. Methods: Mucosal afferent nerves were stimulated by exposing the intestinal mucosa to capsaicin (1.6 mM), which stimulates intestinal external axons. Epithelial cell renewal was investigated in the jejunum by measuring intestinal thymidine kinase (TK) activity, intestinal H-3-thymidine incorporation into DNA, and the number of crypt cells labeled with BrdU. The influence of the external gut innervation was minimized by severing the periarterial nerves. Principal Findings: Luminal capsaicin increased all the studied variables, an effect nervously mediated to judge from inhibitory effects on TK activity or H-3-thymidine incorporation into DNA by exposing the mucosa to lidocaine (a local anesthetic) or by giving four different neurotransmitter receptor antagonists i.v. (muscarinic, nicotinic, neurokinin1 (NK1) or calcitonin gene related peptide (CGRP) receptors). After degeneration of the intestinal external nerves capsaicin did not increase TK activity, suggesting the involvement of an axon reflex. Intra-arterial infusion of Substance P (SP) or CGRP increased intestinal TK activity, a response abolished by muscarinic receptor blockade. Immunohistochemistry suggested presence of M3 and M5 muscarinic receptors on the intestinal stem/progenitor cells. We propose that the stem/progenitor cells are controlled by cholinergic nerves, which, in turn, are influenced by mucosal afferent neuron(s) releasing acetylcholine and/or SP and/or CGRP. In mice lacking the capsaicin receptor, thymidine incorporation into DNA and number of crypt cells labeled with BrdU was lower than in wild type animals suggesting that nerves are important also in the absence of luminal capsaicin, a conclusion also supported by the observation that atropine lowered thymidine incorporation into DNA by 60% in control rat segments. Conclusion: Enteric nerves are of importance in maintaining the intestinal epithelial barrier.
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| 9. |
- Mu, J, et al.
(författare)
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Lithium evokes a more pronounced natriuresis when administered orally than when given intravenously to salt-depleted rats.
- 1999
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Ingår i: Pflügers Archiv : European journal of physiology. - 0031-6768. ; 438:2, s. 159-64
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Tidskriftsartikel (refereegranskat)abstract
- The effects on renal sodium excretion of giving lithium chloride (LiCl; 0.75 mmol per kg body mass) by gavage or intravenously were investigated. The experiments were carried out on Wistar-Kyoto (WKY) or spontaneously hypertensive (SHR) rats in metabolic cages. The rats had been on a low-salt diet for 4 days. Urine excretion of water, sodium and potassium was followed before and for 24 h after giving LiCl. An oral dose of LiCl evoked a more pronounced renal sodium excretion in either strain of rat as compared to that following intravenous administration, in agreement with previous observations of the effects of giving sodium chloride. Choline chloride (1.5 mmol per kg body mass) given by gavage to WKY rats or SHR evoked no change in the renal excretion of sodium. Based on the results of the present study and on observations reported in the literature, we propose that the intestinal tract contains a sodium "sensor", which upon activation releases a natriuretic factor to cause renal sodium excretion. The present results indicate that the proposed "sensor" is sensitive to lithium but not chloride ions.
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| 10. |
- Nilsson, Holger, 1956, et al.
(författare)
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Björn Folkow (1921-2012)
- 2012
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Ingår i: Acta Physiologica. - 1748-1708. ; 206:4, s. 251-254
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
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