Why do neurotransmitters act like growth factors?

Abstract

It is now well established that neurotransmitters act as growth-regulatory signals for neuronal and non-neuronal cells of both primitive and higher organisms, where they control cell proliferation, motility, survival, growth, differentiation, and gene expression. Many of these actions are reminiscent of the actions of other growth-regulatory signals such as growth factors, neurotrophins, and proto-oncogenes. How, then, do neurotransmitters exert these effects? Although some information is available concerning second messengers activated by these neurotransmitters in developing cells, little is known about subsequent steps involving signal transduction cascades leading to their final outcomes. This review attempts to provide testable hypotheses regarding possible cellular and molecular mechanisms downstream of second messengers activated by neurotransmitters, based on recent insights into signal transduction cascades activated by classical growth-regulatory signals. In many cases, there are clear points of convergence between these pathways, raising the interesting possibility that neurotransmitters and other growth-regulatory signals may cooperate to regulate developmental functions of cells and tissues.