The structures, functions and distributions of receptors and transporters in the nervous system and neuroendocrine tissues are being studied. The distributions of serotonin, dopamine, norepinephrine transporters and vesicular monoamine transporters have been determined using in situ hybridization histochemistry in adult and embryonic rat tissues. The serotonin transporter is transiently expressed in peripheral and central sensory pathways and in limbic structures of the brain perinatally implying the existence of a critical period for regulating serotonin in the developing brain. The presence of serotonin transporter in numerous sites throughout the embryo suggests a role for this transporter and serotonin, itself, in morphogenesis and differentiation. A novel dopaminergic system which synthesizes, stores and releases dopamine in the gastrointestinal tract is important for protecting mucosa from acid and digestive enzymes. Vesicular monoamine transporters (VMATs), responsible for packaging serotonin, dopamine, no- repinephrine and epinephrine, were identified perinatally in neurons of limbic structures associated with affective disorders. These cells do not synthesize monoamines but are targets of monoaminergic innervation, suggesting an unappreciated role for monoamines in the synaptic connections of the limbic system. Following immobilization stress, levels of serotonin transporter mRNA were increased in the hypothalamus where serotonin regulates neuroendocrine responses, indicating a possible alteration in serotonergic neurotransmission. Serine/threonine phosphorylation appears to enhance serotonin re-uptake in a neuroblastoma model by post-translational mechanisms. An additional non-coding exon has been identified in the serotonin transporter gene, suggesting that transcriptitonal regulation may be more complex than previously appreciated. This novel exon is alternatively spliced at the 5' untranslated region, raising the possibility for translational regulation.
