Induction of neurite outgrowth of PC12 cells by an inhibitor of vacuolar H(+)-ATPase, bafilomycin A1.

Bafilomycin A1, a selective inhibitor of vacuolar H(+)-ATPase, induced neurite outgrowth of PC12 cells dose- and time-dependently: more than 50% of the cells extended neurite-like spikes after 24 h treatment with 100 nM bafilomycin A1. Its dose-response ran roughly parallel to that of a bafilomycin A1-induced lysosomal pH increase. It was inhibited by LiCl, an inhibitor of the phosphorylation of microtubule-associated proteins and, like nerve growth factor (NGF)-induced neurite outgrowth, it was also inhibited by cycloheximide and actinomycin D. But, unlike the NGF-effect, it was not associated with rapid induction of c-fos.