The structures, functions and distributions of receptors and transporters in the nervous system and neuroendocrine tissues are being studied. Two glycine transporter variants arise from alternative promoter usage and may be developmentally regulated. 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. A novel dopaminergic system which synthesizes, stores and releases dopamine in the gastrointestinal tract is important for protecting mucosa from acid and digestive enzymes. The presence of serotonin transporter in numerous sites throughout the embryo suggests a role for this transporter and serotonin, itself, in morphogenesis and differentiation. 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. Vesicular monoamine transporters (VMATs), responsible for packaging serotonin, dopamine, norepinephrine and epinephrine, were identified 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 limbic system. Maintenance of dopamine transporter and tyrosine hydroxylase mRNA levels requires nigrostriatal or striatonigral innervation in some dopaminergic cell groups but not in the hypothalamus. Following immobilization stress, levels of dopamine transporter and tyrosine hydroxylase mRNAs were increased in several brain regions. Activation of 5HT2 receptors by the hallucinogen and substituted amphetamine, DOI, stimulated serotonin transport activity through a cGMP- dependent pathway in rat brain slices. The level of phosphorylation of the serotonin transporter is enhanced by increasing cGMP levels, suggesting that phosphorylation may play a role in receptor-mediated regulation of the serotonin transporter. The gene for the serotonin transporter has been isolated and transcriptional regulation is being studied. The serotonin transporter mRNA is differentially spliced at the 5' untranslated region, raising the possibility for translational regulation
