Long-Term Treatment of PC12 Pheochromocytoma with Dibutyryl Cyclic Amp Increases Biopterin Content in the Cells but Decreases that in the Medium

Abstract

Pheochromocytoma PC12 is known to be a nerve growth factor (NGF)-responsive cell line: upon the addition of NGF, cells are induced to differentiate into sympathetic neuron-like cells from the chromaffin cell-like phenotype¹. Tetrahydrobiopterin (BH₄) and total biopterin (BP) contents and GTP cyclohydrolase activity in PC12 and PC12h cells, a subclone of PC12, were increased by the treatment with NGF^2–5. Other agents which elevate the intracellular cAMP such as dBcAMP, forskolin and cholera toxin were also able to show the similar effect as NGF^2–6. Although both NGF and dBcAMP increased the cellular BP content and the cyclohydrolase activity, they showed the quite different effect on DA level of PC12h cells: dBcAMP stimulated the DO production but unexpectedly decreased the cellular DA level of the subclone^7,8. In both PC12 and PC12h cells, DA content in the medium was extremely increased by dBcAMP treatment. We found that in both cell lines vesicular membrane transport of monoamines was inhibited by the elevation of intracellular cAMP thus increasing the outward flow of DA and inhibiting its reuptake^8,*.