Substance P gene expression in sympathetic neurons is regulated by neuron/support cell interaction.

In agreement with previous findings, the presence of support cells was found to increase the level of preprotachykinin (i.e. substance P-encoding) mRNA in cultures of sympathetic neurons. Treatment of neuron-only cultures, which did not express detectable levels of preprotachykinin mRNA, with conditioned medium from support cell-only cultures, also increased the level of preprotachykinin mRNA. This elevation in substance P gene expression was reflected in a 2-fold increase in the number of substance P-like immunoreactive neurons. In contrast, treatment of neuron-only cultures with conditioned medium from co-cultures of sympathetic neurons and support cells did not increase the level of preprotachykinin mRNA or the number of neurons containing substance P-like immunoreactivity. These observations suggest that while support cells release a soluble factor(s) capable of inducing substance P expression in sympathetic neurons, the production or action of this factor(s) is inhibited by the interaction between support cells and sympathetic neurons. Thus, by interacting with non-neuronal cells in their environment, sympathetic neurons appear to play an active role in determining which neurotransmitter phenotype they express.