Neurotransmitters as growth regulatory signals: role of receptors and second messengers

In the adult nervous system, neurotransmitters act as chemical mediators of intercellular communication by the activation of specific receptors and second messengers in postsynaptic cells. This specialized role may have evolved from more primitive functions in lower organisms where these substances were used as both intra- and intercellular signalling devices. This view derives from the finding that a number of 'classical' neurotransmitters are present in primitive organisms and early embryos in the absence of a nervous system, and pharmacological evidence that these substances regulate morphogenetic activities such as proliferation, differentiation, cell motility and metamorphosis. These phylogenetically old functions may be reiterated in the developing nervous system and in the humoral functions of neurotransmitters outside the nervous system. This review will provide evidence for this hypothesis based on the commonality of signal transduction mechanisms used in primitive organisms, early embryos and non-neuronal cells, and relate these relationships to the functions of neurotransmitters in the developing nervous system. This discussion has generally been limited to neurotransmitters where non-neuronal functions have been studied and information regarding the involvement of receptors and second messenger pathways is available.