Stimulatory Effects of Substance P on Neurite Extension and Cyclic Amp Levels in Cultured Neuroblastoma Cells

Synthetic substance P initially increased cyclic AMP levels and subsequently induced neurite extension in cultured neuroblastoma N 18 cells. The magnitude of these effects depended on the concentration of fetal calf serum (FCS) in the culture medium, being more evident in the presence of a lower (0.1%) concentration of FCS. In Eagle's medium containing 0.1% FCS, low concentrations of substance P (10 −7 ‐10 −5 M) increased cyclic AMP levels and stimulated neurite extension. In Eagle's medium containing 5%FCS, both substance P at concentrations of 10 −5 ‐10 −3 M and dibutyryl cyclic AMP at concentrations of 10 −4 ‐10 −2 M increased cyclic AMP levels and stimulated neurite extension. The activities of acetylcholinesterase, (Na + + K + )‐, HCO 3 − and Mg 2+ ‐stimulated‐ATPase were also increased. Cell growth was inhibited. Substance P at concentrations of 10‐ 7 ‐10 −5 M also stimulated the adenylate cyclase activity of a particulate fraction of N 18 in a concentration‐dependent manner.