Acute Hypoxia Induces Enkephalin Production and Release in an Adrenergic Cell Line Model of Neonatal Chromaffin Cell Responses to Hypoxic Stress.

Objective: Prior to maturation of the human sympathetic nervous system, the neonatal adrenal medulla senses and responds to hypoxia. In addition to catecholamine release, the adrenal medulla synthesizes and stores opioid peptides, notably enkephalin (ENK). However, it is not known whether acute hypoxia evokes adrenal ENK production and release, as seen in the central nervous system (CNS).

Transcriptional silencing of glucocorticoid-inducible phenylethanolamine N-methyltransferase expression by sequential signaling events.

Specific arrays and timing of environmental cues including glucocorticoids, neurotrophic factors and intracellular messengers influence phenotype expression in developing chromaffin cells or sympathetic neurons. Although the two lineages are closely related, only adrenergic chromaffin cells express phenylethanolamine N-methyltransferase (PNMT), the enzyme that synthesizes epinephrine, while neurons and noradrenergic chromaffin cells are PNMT-negative. It remains unclear to what extent the ability to express PNMT is determined by environmental cues versus intrinsic heterogeneity already present in ganglionic and adrenal precursors.

Nicotine stimulates expression of the PNMT gene through a novel promoter sequence.

Transcription of the gene encoding the epinephrine-synthesizing enzyme phenylethanolamine N-methyltransferase (PNMT, E.C. 2.

Hypoxia activates multiple transcriptional pathways in mouse pheochromocytoma cells.

Mouse pheochromocytoma cells (MPCs) provide an excellent model system for investigating the effects of hypoxia on catecholamine enzyme genes and on transcription factors mediating stress responses. RT-PCR detects rapid, transient increases in PNMT mRNA in hypoxic MPC 712 cells. Additionally, elevation of mRNAs encoding transcription factors hypoxia inducible factor 1 (HIF-1) alpha subunit and Egr-1 are evident within 60 min incubation in anoxia.