Dual effects of endothelin-1 on neurite outgrowth induced by 12-O-tetradecanoylphorbol-13-acetate.

The vasoactive peptide endothelin-1 (ET-1) was found to bind to a single class of binding sites in chick embryonic sensory ganglia with a Kd of 67 +/- 5 pM. Treatment of ganglia explants with 100 pM ET-1 did not affect neuronal development, but when added together with 12-O-tetradecanoylphorbol-13-acetate (TPA) a synergistic stimulation of neurite outgrowth was observed. In contrast, 10 nM ET-1 inhibited TPA-induced neurite outgrowth. Both the stimulatory and inhibitory effects were not blocked by nifedipine, a Ca2+ channel blocker. These results suggest that ET-1 can modulate the process of neurite outgrowth and its effects are not dependent on voltage-gated Ca2+ channels.