Differential Regulation of Nicotinic Acetylcholine Receptors in PC12 Cells by Nicotine and Nerve Growth Factor
Open Access
- 18 September 2003
- journal article
- Published by American Society for Pharmacology & Experimental Therapeutics (ASPET) in Molecular Pharmacology
- Vol. 64 (4), 974-986
- https://doi.org/10.1124/mol.64.4.974
Abstract
Tyrosine hydroxylase (TH) is the initial and rate-limiting enzyme in the synthesis of the neurotransmitter dopamine. TH is inhibited and nitrated at tyrosine residues in vitro by the reactive nitrogen species peroxynitrite and nitrogen dioxide (NO2) and in vivo by drugs that damage dopamine neurons. Tetrahydrobiopterin, which is the essential cofactor for TH and is concentrated in dopamine neurons, completely blocks nitration of tyrosine residues in TH caused by peroxynitrite or NO2. Various tetrahydro- and dihydro-analogs of tetrahydrobiopterin, including 6,7-dimethyl-tetrahydropterin, 6-methyl-tetrahydropterin, 6-hydroxymethyl-tetrahydropterin, tetrahydropterin, 7,8-dihydrobiopterin, 7,8-dihydroxanthopterin, and sepiapterin, also prevent nitration of tyrosines caused by the reactive nitrogen species. Biopterin and pterin, the fully oxidized forms of the pterin molecule, fail to block peroxynitrite- or NO2-induced nitration of TH. Reduced pterins prevent neither the inhibition of TH activity nor cysteine modification caused by peroxynitrite or NO2, despite blocking tyrosine nitration. However, dithiothreitol prevents and reverses these effects on TH of tetrahydrobiopterin and reactive nitrogen species. Using an enhanced green fluorescent protein-TH fusion construct as a real-time reporter of intracellular tyrosine nitration, tetrahydrobiopterin was found to prevent NO2-induced tyrosine nitration in intact cells but to leave TH activity inhibited. These results indicate that tetrahydrobiopterin prevents the tyrosine-nitrating properties of peroxynitrite and NO2. Tetrahydrobiopterin-derived radical species formed by reaction with reactive nitrogen species may account for inhibition of TH via mechanisms that do not involve tyrosine nitration.Keywords
This publication has 30 references indexed in Scilit:
- Chronic nicotine administration does not increase nicotinic receptors labeled by [125I]epibatidine in adrenal gland, superior cervical ganglia, pineal or retinaJournal of Neurochemistry, 2003
- Measuring nicotinic receptors with characteristics of α4β2, α3β2 and α3β4 subtypes in rat tissues by autoradiographyJournal of Neurochemistry, 2002
- Regulation of α3 Nicotinic Acetylcholine Receptor Subunit mRNA Levels by Nerve Growth Factor and Cyclic AMP in PC12 CellsJournal of Neurochemistry, 2000
- Differential Regulation of Neuronal Nicotinic Receptor Binding Sites Following Chronic Nicotine AdministrationJournal of Neurochemistry, 1997
- Assembly of Human Neuronal Nicotinic Receptor α5 Subunits with α3, β2, and β4 SubunitsPublished by Elsevier ,1996
- Rapid Communication: Nerve Growth Factor Increases the Transcriptional Activity of the Rat Neuronal Nicotinic Acetylcholine Receptor β4 Subunit Promoter in Transfected PC12 CellsJournal of Neurochemistry, 1994
- The Diversity of Neuronal Nicotinic Acetylcholine ReceptorsAnnual Review of Neuroscience, 1993
- Nerve growth factor enhances [3H]nicotine binding to a nicotinic cholinergic receptor on PC 12 cellsEndocrinology, 1992
- Evidence that Tobacco Smoking Increases the Density of (−)‐[3H]Nicotine Binding Sites in Human BrainJournal of Neurochemistry, 1988
- Functional acetylcholine receptor in PC12 cells reacts with a monoclonal antibody to brain nicotinic receptorsNature, 1987