Regulation of GTP cyclohydrolase i and dihydropteridine reductase in rat pheochromocytoma PC 12 cells

Rong Sen Shen, Yixian Zhang, J. Regino Perez-Polo

    Research output: Contribution to journalArticle

    5 Scopus citations

    Abstract

    The addition of 8-bromo cyclic AMP, forskolin, theophylline, and 3-isobutyl-1-methylxanthine to the medium of PC 12 cells resulted in an increase in GTP cyclohydrolase I activity, but had no effect on dihydropteridine reductase activity, except theophylline which caused a decrease in dihydropteridine reductase activity at 96 h. GTP cyclohydrolase I activity peaked at 24 h and returned to normal 96 h after drug treatment. Cycloheximide decreased GTP cyclohydrolase I activity at 48 and 96 h, but had little effect on dihydropteridine reductase activity. The addition of reserpine selectively increased only GTP cyclohydrolase I activity. The addition of tetrahydrobiopterin and sepiapterin, however, coordinately inhibited both GTP cyclohydrosase I and dihydropteridine reductase activities. It appears that GTP cyclohydrolase I activity in PC 12 cells is regulated by cyclic AMP stimulation and by end-product inhibition, whereas dihydropteridine reductase activity is only subject to pterin inhibition.

    Original languageEnglish (US)
    Pages (from-to)119-126
    Number of pages8
    JournalJournal of Enzyme Inhibition and Medicinal Chemistry
    Volume3
    Issue number2
    DOIs
    StatePublished - Jan 1 1989

    Keywords

    • Cyclic AMP
    • Dihydropteridine reductase
    • GTP cyclohydrolase
    • PC 12
    • Pheochromocytoma
    • Tetrahydrobiopterin

    ASJC Scopus subject areas

    • Pharmacology
    • Drug Discovery

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