Tumor Necrosis Factor Modulates the Inactivation of Catecholamine Secretion in Cultured Sympathetic Neurons

Abstract

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-β (0.14-0.7 nM) or recombinant human tumor necrosis factor-α (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.