Effects of p-bromophenacyl bromide on neurite growth at different levels of nerve growth factor

We have previously been shown that the phospholipase inhibitor p-bromophenacyl bromide (BPB) modifies neurite morphology and growth rate in rat dorsal root ganglion explants. Neurite extension is stimulated by 2.5 X 10(-7) M BPB but it is prevented by concentrations higher than 10(-5) M. Under our experimental conditions, no neurites appeared in the absence of added nerve growth factor (NGF). Therefore, we have tested the effect of a low BPB concentration at different levels of exogenous NGF. Thoracic and lumbar ganglia were obtained from 19.5-day-old fetal rats and were cultured for 24 h on a polyornithine substrate. Neurite growth and development of a dense halo were NGF-dependent in both ganglionic populations; however, each of them showed a characteristic dose-response curve. Incubation with BPB induced neurites in the absence of added NGF and stimulated their growth when low levels of this factor were added. In lumbar ganglia incubated with higher levels of NGF, BPB had no detectable effects. On the contrary, similarly treated thoracic ganglia showed an inhibition of neurite extension. Our findings suggest a relationship between the effects of BPB and the initial, membrane-activating actions of NGF.