Multiple Pathways in Regulation of Dopamine β-Hydroxylase

Publisher Summary

DBH is localized in membrane-bound (77-kDa) and soluble (73-kDa) forms in neurosecretory vesicles of the noradrenergic neurons of the central and peripheral nervous systems and in the chromaffin granules of the adrenal medullary cells. Experiments from several groups reveal that both forms of DBH arise from a single translational product. Dopamine β-hydroxylase (DBH) catalyzes the hydroxylation of dopamine to form norepinephrine. The expression of DBH is elevated in vivo in response to a variety of transsynaptic signals, hormones, growth factors, and stress. There is now a large body of experiments demonstrating that with prolonged conditions that stimulate catecholamine biosynthesis, the expression of DBH also is markedly elevated. In vivo, DBH gene expression has been shown to be elevated by several important physiological and pharmacological stimuli. These include treatment of rats with reserpine, or nicotine or electrical preganglionic stimulation. Exposure to stress markedly activates DBH gene expression. Using electrophoretic mobility shift assays, it has been shown that the transcription factors are not identical to those reported to interact with its human analogue. For example, the human DBH promoter oligonucleotide analogous to DBH-1 has been shown to bind YY1.