Regulation of GTP cyclohydrolase I and dihydropteridine reductase in rat pheochromocytoma PC 12 cells.
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 cyclohydrolase 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.
Shen
R S
RS
Department of Human Biological Chemistry & Genetics, University of Texas Medical Branch, Galveston 77550.
Zhang
Y X
YX
Perez-Polo
J R
JR
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology*; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology*; D000310:Adrenal Gland Neoplasms; D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives / Q000494:pharmacology; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology*; D003513:Cycloheximide / Q000494:pharmacology; D004093:Dihydropteridine Reductase / Q000378:metabolism*; D006136:GTP Cyclohydrolase / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism*; D007700:Kinetics; D010673:Pheochromocytoma; D011621:Pteridines / Q000494:pharmacology; D011622:Pterins; D051381:Rats; D012110:Reserpine / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology*
D007527:Isoenzymes; D011621:Pteridines; D011622:Pterins; D005576:Colforsin; D001708:Biopterins; D015124:8-Bromo Cyclic Adenosine Monophosphate; D012110:Reserpine; D003513:Cycloheximide; D013806:Theophylline; C016727:sepiapterin; D004093:Dihydropteridine Reductase; D006136:GTP Cyclohydrolase; C003402:sapropterin; D015056:1-Methyl-3-isobutylxanthine