The striatonigral substance P pathway and dopaminergic mechanisms.

The biosynthesis of 35S-labelled substance P (SP) has been shown in the rat striatum after continuous delivery of [35S]methionine through a push-pull cannula. In vitro and in vivo studies of SP release have demonstrated that release of the peptide depends on nerve activity and is regulated by presynaptic influences. When the 125I-labelled Bolton and Hunter SP derivative was used, specific binding was observed on mesencephalic cells of the mouse embryo in primary cultures and various characteristics of SP receptors could be determined. Finally, the effects of facilitation or prevention of SP transmission in the substantia nigra on the activity of nigrostriatal dopaminergic neurons have been studied in vivo in the cat by measuring dopamine released from nerve terminals and dendrites. The results obtained indicate that the striatonigral SP neurons exert a tonic facilitatory influence on the dopaminergic neurons.