| TNF-alpha hyperpolarizes membrane potential and potentiates the response to nicotinic receptor stimulation in cultured rat myenteric neurones. | |
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MedLine Citation:
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PMID: 15086448 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AIMS: Tumour necrosis factor-alpha (TNF-alpha) plays a central role in the pathophysiology of inflammatory bowel disease. The present experiments were designed to characterize the action of this cytokine on enteric neurones. METHODS: Myenteric ganglia from newborn rats were treated for 20 h with TNF-alpha (100 ng mL(-1)) and studied with the patch-clamp technique. RESULTS: Control neurones showed a membrane potential of -34.6 +/- 2.2 mV (n = 22), whereas TNF-alpha-treated cells exhibited a membrane potential of -50.8 +/- 3.5 mV (n = 25). The depolarization evoked by carbachol (50 microm) was potentiated from 5.2 +/- 0.7 mV (n = 6) in control neurones to 27.5 +/- 2.0 mV (n = 10) in TNF-alpha-treated cells. This effect was mimicked by 1,1-dimethyl-4-phenylpiperazinium iodide, but not by bethanechol. The changes in basal membrane potential and in the nicotinic receptor response were suppressed by the non-selective cyclooxygenase (COX) inhibitor indomethacin (10 microm), and the COX II-specific inhibitor, nimesulide (100 microm), whereas the COX-I selective inhibitor SC-560 (5 microm) and the proteintyrosinekinase inhibitor genistein (50 microm) only partially inhibited the action of TNF-alpha. Staining of the ganglionic cells with an antibody against the transcription factor STAT5 revealed that TNF-alpha induced a nuclear translocation of STAT5 in non-neuronal cells. CONCLUSION: TNF-alpha changes the electrophysiological properties of myenteric neurones via cyclooxygenase metabolites and protein tyrosine phosphorylation; the cells primarily responding to the cytokine seem to be non-neuronal cells in the ganglion culture, which respond with a nuclear STAT5 translocation suggesting an action on gene transcription. |
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Authors:
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M Rehn; T Hübschle; M Diener |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Acta physiologica Scandinavica Volume: 181 ISSN: 0001-6772 ISO Abbreviation: Acta Physiol. Scand. Publication Date: 2004 May |
Date Detail:
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Created Date: 2004-04-16 Completed Date: 2004-07-26 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0370362 Medline TA: Acta Physiol Scand Country: England |
Other Details:
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Languages: eng Pagination: 13-22 Citation Subset: IM |
Affiliation:
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Institute for Veterinary Physiology, University of Giessen, Giessen, Germany. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Animals, Newborn Bethanechol / pharmacology Carbachol / pharmacology Cells, Cultured Cyclooxygenase Inhibitors / metabolism DNA-Binding Proteins / analysis Dimethylphenylpiperazinium Iodide / pharmacology Enzyme Inhibitors / pharmacology Ganglia, Autonomic / cytology, drug effects Genistein / pharmacology Immunohistochemistry / methods Indomethacin / metabolism Intestine, Small / cytology Membrane Potentials / drug effects, physiology Milk Proteins* Muscarinic Agonists / pharmacology Myenteric Plexus / cytology, drug effects Neurons / drug effects, physiology* Nicotinic Agonists / pharmacology Patch-Clamp Techniques / methods Rats Receptors, Nicotinic / physiology* STAT5 Transcription Factor Trans-Activators / analysis Tumor Necrosis Factor-alpha / physiology* |
| Chemical | |
Reg. No./Substance:
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0/Cyclooxygenase Inhibitors; 0/DNA-Binding Proteins; 0/Enzyme Inhibitors; 0/Milk Proteins; 0/Muscarinic Agonists; 0/Nicotinic Agonists; 0/Receptors, Nicotinic; 0/STAT5 Transcription Factor; 0/Trans-Activators; 0/Tumor Necrosis Factor-alpha; 446-72-0/Genistein; 51-83-2/Carbachol; 53-86-1/Indomethacin; 54-77-3/Dimethylphenylpiperazinium Iodide; 674-38-4/Bethanechol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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