We are continuing to study the structural and genetic basis for generating the diversity of neuropeptide/neurotransmitter phenotypes found in the nervous and endocrine systems. This work involves 1) analysis of cis- acting elements determining cell-specific expression and regulation of neuropeptide genes and ii) characterization of the components of neuropeptide/neurotransmitter vesicles responsible for packaging of neurotransmitters and neuropeptides in neuroendocrine cells. 1) A protein kinase C responsive element on the galanin gene, called the GTRE (galanin TPA-responsive element) has been demonstrated to transduce transcriptional activation of the galanin gene in response to both protein kinase C and protein kinase A pathways. 2) The human biogenic amine transporters VMAT1 and VMAT2 have been cloned and sequenced. Similarities and differences between central and peripheral biogenic amine storage in rodents and humans can now be determined in vitro, and used to predict the activity profiles of neuropharmacological agents in man. 3) The rat and human vesicular acetylcholine transporters have been cloned and functionally characterized. The acetylcholine transporter is expressed from the same gene locus as the enzyme choline acetyltransferase, responsible for the biosynthesis of acetylcholine in the cholinergic nervous system.
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