Journal of Neuroscience, Vol 4, 1771-1780, Copyright © 1984 by Society for Neuroscience
Nerve growth factor-mediated enzyme induction in primary cultures of bovine adrenal chromaffin cells: specificity and level of regulation
AL Acheson, K Naujoks and H Thoenen
Primary cultures of bovine adrenal chromaffin cells provide large
quantities of a homogeneous population of target cells for nerve growth
factor (NGF) and, thus, are a suitable system for studying the molecular
mechanism of action of NGF. In this study, we have shown that NGF mediates
the specific induction of the key enzymes in catecholamine biosynthesis,
tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), and
phenylethanolamine-N-methyltransferase (PNMT). Acetylcholinesterase (AChE),
an enzyme which catalyzes the breakdown of acetylcholine, is also induced
by NGF. We have compared NGF-mediated TH and AChE induction and have
provided pharmacological evidence that TH induction involves a
post-transcriptional, polyadenylation-dependent event (blockable by
9-beta-arabinofuranosyladenine but not by alpha- amanitin), whereas AChE
induction requires transcription (blockable by alpha-amanitin). DBH and
PNMT appear to be regulated via the same mechanism as TH. The time course
of TH induction is such that NGF must be continuously present for at least
the first 36 hr (during which time TH levels remain unchanged), and then
the entire increase takes place during the subsequent 12 hr. In contrast,
AChE induction proceeds linearly with time of NGF exposure. These data
suggest that there may be multiple mechanisms by which NGF regulates enzyme
induction. We have also compared the effects of cAMP with those of NGF. As
compared to NGF, cAMP produces a different pattern of enzyme induction (in
addition to TH, DBH, PNMT, and AChE, dopa decarboxylase (DDC) is also
induced), it acts rapidly (a 12-hr exposure produces the full effect), and
it acts only at the transcriptional level (its effects are blocked by
alpha-amanitin). These data provide evidence that cAMP does not act as a
second messenger for NGF with regard to enzyme induction.
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