Tumor necrosis factor modulates the inactivation of catecholamine secretion in cultured sympathetic neurons.
Cytokines exert multiple effects on cellular functions. We studied the effects of cytokines on the calcium-dependent release of catecholamines in cultured neurons from neonatal rat superior cervical ganglia. Incubation of sympathetic neurons with recombinant human interleukin-1 beta (0.14-0.7 nM) or recombinant human tumor necrosis factor-alpha (1 nM) for 24-48 h had no effect on the baseline spontaneous release and the initial K(+)-evoked [3H]norepinephrine release, compared with untreated cells. A repeat K(+)-induced depolarization after 6 min resulted in a decrease of [3H]norepinephrine secretion to 69 +/- 5.8% (n = 11) of the initial secretion in recombinant human tumor necrosis factor-treated cells, but not in control cells. The secretory response was restored when the interval between the two K+ challenges was increased to 10 min. We conclude that the diminished secretory response to a repeat stimulus in recombinant human tumor necrosis factor-treated superior cervical ganglia neurons is due to a prolonged recovery from inactivation of secretion in these cells.
Soliven
B
B
Department of Neurology, University of Chicago, Illinois 60637.
Albert
J
J
D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D011994:Recombinant Proteins; D013564:Sympathetic Nervous System / Q000166:cytology / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D002395:Catecholamines; D016207:Cytokines; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D011188:Potassium; D009638:Norepinephrine