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 journalArticlepeer-review

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 - 1989
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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