Figure 6.

BDNF and GDNF are the predominant NRG-releasing factors produced by cultured Schwann cells. A, Specific antagonists block recombinant neurotrophic factor induction of NRG release from cultured neurons. Soluble fusion protein antagonists for BDNF (TrkBFc) and NT-3 (TrkCFc) as well as blocking antibodies against BDNF and GDNF were tested for their ability to block NRG release from DRG sensory neurons using 100 ng/ml BDNF, NT-3, or GDNF. A second α-GDNF antibody had similar blocking ability (data not shown). PMA (to stimulate protein kinase C) and BSA were used as positive and negative controls, respectively. NRG release was measured from duplicate samples with the bioassay as described previously and expressed as mean ± 1 SD. B, When the same antagonists were preincubated with SCCM, NRG release from DRG sensory neurons was effectively inhibited by TrkBFc and the BDNF and GDNF antibodies but not the TrkCFc antagonist. Combinations of the BDNF and GDNF antagonists maximally blocked the ability of SCCM to promote neuronal NRG release, suggesting an additive effect by BDNF and GDNF. Triplicate samples were measured with the bioassay, and statistical significance was calculated using a Student's t test (^*p < 0.05).