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CONCOMITANT ELEVATION OF TYROSINE HYDROXYLASE AND DOPAMINE BETA‐HYDROXYLASE BY CYCLIC AMP IN CULTURED MOUSE NEUROBLASTOMA CELLS 1
Author(s) -
Waymire Jack C.,
GilmerWaymire Katrina,
Boehme Richard E.
Publication year - 1978
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1978.tb07843.x
Subject(s) - tyrosine hydroxylase , medicine , endocrinology , dopamine , tyrosine 3 monooxygenase , chemistry , monoamine oxidase , biology , biochemistry , enzyme
— The effects of cyclic AMP analogues and of phosphodiesterase inhibitors were investigated in neuroblastoma cells (NBD‐2) cloned from the C‐1300 tumor. 8Br‐cAMP and phosphodiesterase inhibitors that elevated cAMP induced large (greater than 15 fold) and specific increases in tyrosine hydroxylase and dopamine beta‐hydroxylase activity. In contrast, catechol O ‐methyltransferase, monoamine oxidase and aromatic‐ l ‐amino‐acid decarboxylase were unaffected by the cAMP altering drugs. Similarly, AChE was unaffected and only a small increase in choline acetyltransferase (3 fold) was observed. The increases in tyrosine hydroxylase and dopamine beta‐hydroxylase were similar with respect to dose response relationships and with respect to time course of onset. Only those phosphodiesterase inhibitors that elevated cAMP (papaverine and Ro20‐1724 as opposed to theophylline) were effective in elevating tyrosine hydroxylase and dopamine beta‐hydroxylase. Further, the doses optimal for elevating cAMP coincided with the optimal doses for elevating the two enzymes. Theophylline had no influence either upon NBD‐2 cell cAMP levels or upon tyrosine hydroxylase and dopamine beta‐hydroxylase activity. The changes in protein synthesis rates produced by the cAMP altering drugs were temporally distinct from the changes in either tyrosine hydroxylase or dopamine beta‐hydroxylase. These results suggest that the intracellular messenger compound cAMP is involved in the specific regulation of both tyrosine hydroxylase and dopamine beta‐hydroxylase in adrenergic cells.