Shen R S, Zhang Y X, Perez-Polo J R
Department of Human Biological Chemistry & Genetics, University of Texas Medical Branch, Galveston 77550.
J Enzyme Inhib. 1989;3(2):119-26. doi: 10.3109/14756368909030370.
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.
向PC 12细胞培养基中添加8-溴环磷酸腺苷、福斯高林、茶碱和3-异丁基-1-甲基黄嘌呤会导致鸟苷三磷酸环化水解酶I活性增加,但对二氢蝶啶还原酶活性没有影响,不过茶碱在96小时时会导致二氢蝶啶还原酶活性降低。鸟苷三磷酸环化水解酶I活性在24小时达到峰值,并在药物处理后96小时恢复正常。放线菌酮在48小时和96小时降低了鸟苷三磷酸环化水解酶I活性,但对二氢蝶啶还原酶活性影响很小。利血平的添加仅选择性地增加了鸟苷三磷酸环化水解酶I活性。然而,添加四氢生物蝶呤和司来吉兰会协同抑制鸟苷三磷酸环化水解酶I和二氢蝶啶还原酶活性。PC 12细胞中的鸟苷三磷酸环化水解酶I活性似乎受环磷酸腺苷刺激和终产物抑制的调节,而二氢蝶啶还原酶活性仅受蝶呤抑制。