Document Detail

TNF-alpha hyperpolarizes membrane potential and potentiates the response to nicotinic receptor stimulation in cultured rat myenteric neurones.
MedLine Citation:
PMID:  15086448     Owner:  NLM     Status:  MEDLINE    
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.
M Rehn; T Hübschle; M Diener
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Acta physiologica Scandinavica     Volume:  181     ISSN:  0001-6772     ISO Abbreviation:  Acta Physiol. Scand.     Publication Date:  2004 May 
Date Detail:
Created Date:  2004-04-16     Completed Date:  2004-07-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0370362     Medline TA:  Acta Physiol Scand     Country:  England    
Other Details:
Languages:  eng     Pagination:  13-22     Citation Subset:  IM    
Institute for Veterinary Physiology, University of Giessen, Giessen, Germany.
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MeSH Terms
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
Receptors, Nicotinic / physiology*
STAT5 Transcription Factor
Trans-Activators / analysis
Tumor Necrosis Factor-alpha / physiology*
Reg. No./Substance:
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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