Neurotrophins stimulate the release of dopamine from rat mesencephalic neurons via Trk and p75Lntr receptors.

We analyzed the short term effect of neurotrophins on mesencephalic neuronal cultures of embryonic (E14) rats with respect to which receptors mediate the actions. Brain-derived neurotrophic factor (BDNF) or neurotrophin-3 enhanced within minutes in a dose-dependent manner (2, 20, 100 ng/ml for 5 min) depolarization-induced (KCl, 30 mM 5 min) and basal dopamine release, but nerve growth factor (NGF) was only effective at high doses (100 ng/ml). The effect of BDNF, but not of NGF, was blocked by K252a or K252b. BDNF, but not NGF, phosphorylated trkB receptors. The NGF-induced, but not the BDNF-induced effect upon the release of dopamine was blocked by anti-p75 antibody MC192. C2-ceramide, an analogue of ceramide, the second messenger of the sphingomyelin pathway, and sphingomyelinase itself induced a release of dopamine comparable with the effect of NGF. NGF, but not BDNF, increased ceramide production. In addition, simultaneous treatment with BDNF and NGF led to a partial prevention of the NGF-stimulated, p75(Lntr)-mediated effect. We conclude that BDNF stimulates the release of dopamine by activation of the trkB receptor, whereas NGF affects the release via the p75(Lntr) receptor inducing the sphingomyelin pathway.