Tumor necrosis factor-alpha regulates nicotinic responses in mixed cultures of sympathetic neurons and nonneuronal cells.
It is recognized that tumor necrosis factor-alpha (TNF-alpha), a pleiotropic cytokine, influences hormone secretion and transmitter release from central neurons. To examine the role of TNF-alpha as a modulator of autonomic function of the PNS, we measured [3H]norepinephrine ([3H]NE) secretion evoked by 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), a nicotinic agonist, in cultures from neonatal rat superior cervical ganglia (SCG). We found that (1) DMPP-evoked [3H]NE secretion was enhanced in SCG mixed cultures treated for 48 h with recombinant human TNF-alpha (rhTNF-alpha) plus rat interferon-gamma (IFN-gamma) but not in cultures treated with either cytokine alone; (2) an increase in [3H]NE secretion was also observed in mixed cultures treated with recombinant murine TNF-alpha (rmTNF-alpha) alone; and (3) the presence of nonneuronal cells or soluble factors released by them was required for the effect of these cytokines on secretion. Electrophysiologic experiments revealed an increase in nicotinic receptor current density in neurons from mixed cultures treated with rhTNF-alpha plus IFN-gamma or with rmTNF-alpha when compared with control cultures. We conclude that prolonged exposure to rhTNF-alpha plus IFN-gamma or rmTNF-alpha regulates nicotinic responses in SCG cultures via a soluble factor or factors secreted by nonneuronal cells.
Soliven
B
B
Department of Neurology, University of Chicago, Illinois 60637.
Wang
N
N
D000818:Animals; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003584:Cytological Techniques; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004553:Electric Conductivity; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D009538:Nicotine / Q000819:agonists / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha; D004246:Dimethylphenylpiperazinium Iodide; D009538:Nicotine; D007371:Interferon-gamma; D011188:Potassium