Drug-induced regulation of neuroactive peptide precursor gene expression -Neuropeptide Y and enkephalin A precursor genes-

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Neuropeptide Y(NPY)and enkephalin A(ENK)are widely distributed and most abundant neuropeptides in neurones in the central nervous system. The processed peptides are important cotransmitter/neuromodulators in the synaptic tr ansmission. We investigated and elucidated the following facts.1. The modulation of synaptic transmission by these neuropeptides is due to the change in expression of the precursor genes, followed by the change in peptide level.2. Because the -expression of the neuropeptide precursor genes is modulated by neural activity in vivo, the investigation of this mechanism can clarify the synaptic plasticity of neural cells.3. Neuroactive drugs, such as antihypertensive drugs and adrenergic agents, change the expression of these precursor gene at the transcriptional level by transsynaptic neural activity and through neurotransmitter receptors, which results in modulation of the synaptic transmission.4. Nuclear run-on and chloramphenicol acetyltransferase assays clearly indicated that the change in gene expression is mainly due to that at the transcriptional level.5. We have identified Ca response element. cAMP response element, glucocorticoid element and NGF response element in the promoter regions.6. Thus these molecular biological procedures have been clarified the new mechanism of neuroactive drugs at the gene expression of neural genes.