Time requirement for the single steps of trans-synaptic induction of tyrosine hydroxylase in the peripheral sympathetic nervous system

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The trans-synaptic induction of tyrosine hydroxylase (TH) in the peripheral sympathetic nervous system is a slow process. The present experiments were performed to establish the time required to accomplish the single steps of TH induction, i.e. duration of the increased preganglionic activity and of the resulting changes at the transcription and translation levels. An intermittent swimming stress of 1 h was sufficient to lead to a statistically significant (P<0.05) increase in TH activity in the adrenal medulla 48 h later. A 2-h swimming stress was necessary to produce the same effect in the superior cervical and stellate ganglia. Administration of a ganglionic blocking agent (chlorisondamine 5 mg/kg i.p) immediately after and 1 h after termination of the swimming stress significantly (P<0.05) reduced the increase in TH activity, whereas 2 h after the stress this drug was without effect, indicating that the enhanced preganglionic activity exceeded the end of the swimming stress by 1 to 2 h, or that normal ganglionic transmission represents a permissive prerequisite for the initiation of the induction process. Treatment of rats with a single dose of actinomycin D (0.8 mg/kg s.c.) immediately before or after the swimming stress completely abolished the increase in the TH activity. If actinomycin D was injected 6 or 12 h after the stress the increase in TH was reduced but not abolished, whereas treatment with actinomycin D after 24 h had no effect. Thus, the transcription phase of trans-synaptic induction seems to be completed by 24 h after stress. The fact that an increased rate of TH synthesis continued up to 48 h implies that the turnover of the (messenger) RNA involved is slow enough to allow an increased synthesis of TH 24 h beyond the termination of the regulatory step at the transcription level.