Upregulation of catecholamine biosynthetic enzymes by nitric oxide.

Nitric oxide (NO) is recognized as an essential intercellular messenger in central and peripheral nervous systems. In the present study, whether NO exerts effects on catecholamine (CA) biosynthetic enzymes was determined in primary cultured bovine chromaffin cells. The NO generators sodium nitroprusside (SNP) and S-nitroso-N-acetyl-D,L-penicillamine, in a dose-dependent manner, upregulated transcript levels of tyrosine hydroxylase, dopamine beta-hydroxylase, and phenylethanolamine N-methyltransferase, accompanied by long-term increases in their enzyme activities and the intracellular CA levels. The SNP effect was diminished by co-treatment with LY83583, an inhibitor of soluble guanylate cyclase, or H-8, a cyclic GMP (cGMP)-dependent protein kinase inhibitor. Co-treatment with 8-Br-cGMP did not increase further the expression of these enzyme genes induced by SNP. Taken together, the data suggest that NO leads to long-term upregulation of the CA system via induction of the genes involved and that this is mediated by cGMP-dependent signaling pathway. Copyright 2003 Wiley-Liss, Inc.