title: Regulation of GTP cyclohydrolase I gene expression and tetrahydrobiopterin content by nerve growth factor in cultures of superior cervical ganglia.
abstract: Monolayer cultures of superior cervical ganglia free of support cells were maintained in the presence of 100 ng/ml 7S-NGF for 4 days. The concentration of NGF was then changed to between 50 and 400 ng/ml and cultures continued for an additional 7 days. Tetrahydrobiopterin (BH4) content, GTP cyclohydrolase (GTPCH) enzyme activity and mRNA levels were then determined. All three of these measures were found to be elevated between 2- to 4-fold by treatment with increasing concentrations of NGF. Tyrosine hydroxylase (TH) enzyme activity and mRNA levels were increased from 8 to 13-fold by these same treatments. These results indicate that the content of BH4 within sympathetic neurons can be regulated by NGF receptor-mediated changes in GTPCH gene expression. Moreover, concomitant increases in TH enzyme activity and BH4 content demonstrate a coordinated regulation by NGF of this enzyme and its essential cofactor.
authors.affiliation: Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI 48201, USA.
authors.forename: K
authors.initials: K
authors.lastname: Hirayama
authors.forename: G
authors.initials: G
authors.lastname: Kapatos
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives* / Q000378:metabolism; D002478:Cells, Cultured; D006136:GTP Cyclohydrolase / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017783:Superior Cervical Ganglion / Q000187:drug effects* / Q000378:metabolism
chemical_list: D009414:Nerve Growth Factors; D001708:Biopterins; D006136:GTP Cyclohydrolase; C003402:sapropterin