Journalartikel

Jahr der Veröffentlichung: 2004

Seiten: 13-22

Zeitschrift: Acta physiologica Scandinavica

Bandnummer: 181

Heftnummer: 1

ISSN: 0001-6772

DOI Link: https://doi.org/10.1111/j.1365-201X.2004.01269.x

Verlag: Blackwell

Abstract: 

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 muM) 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 muM), and the COX II-specific inhibitor, nimesulide (100 muM), whereas the COX-I selective inhibitor SC-560 (5 muM) and the proteintyrosinekinase inhibitor genistein (50 muM) 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.

Harvard-Zitierstil: Rehn, M., Hübschle, T. and Diener, M. (2004) TNF-alpha hyperpolarizes membrane potential and potentiates the response to nicotinic receptor stimulation in cultured rat myenteric neurones, Acta physiologica Scandinavica, 181(1), pp. 13-22. https://doi.org/10.1111/j.1365-201X.2004.01269.x

APA-Zitierstil: Rehn, M., Hübschle, T., & Diener, M. (2004). TNF-alpha hyperpolarizes membrane potential and potentiates the response to nicotinic receptor stimulation in cultured rat myenteric neurones. Acta physiologica Scandinavica. 181(1), 13-22. https://doi.org/10.1111/j.1365-201X.2004.01269.x