[Effect of dibutyryl cyclic AMP on the GTP cyclohydrolase activity and tetrahydrobiopterin content of pheochromocytoma PC12h cells].

Abstract

Effect of dibutyryl cyclic AMP (dBcAMP)-treatment of pheochromocytoma PC12h cells, a subclonal line of PC12, on the GTP cyclohydrolase activity and biopterin (BP) content of the cells was studied. Both the enzyme activity and BP content of the cells were transiently increased by dBcAMP treatment with both the maximal activity and content at 1 to 2 days after the treatment was started. The effect of dBcAMP was not detectable at concentrations lower than 10 microM and reached the plateau level at 500 microM in a dose-dependent manner. EC50 values of dBcAMP for increasing the enzyme activity and BP content were the same, approximately 200 microM. The dBcAMP-induced increase in both the GTP cyclohydrolase activity and BP content of the PC12h cells was completely blocked by cycloheximide, a protein synthesis inhibitor, suggesting that the effect of dBcAMP is mediated by the synthesis of some protein, most probably GTP cyclohydrolase itself.