Summary
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.
Similar content being viewed by others
References
Black, I. B., Hendry, I. A., Iversen, L. L.: Differences in the regulation of tyrosine hydroxylase and Dopa decarboxylase in sympathetic ganglia and adrenal. Nature (Lond.) 231, 27–29 (1971)
Håkanson, R., Owman, Ch.: Pineal dopa decarboxylase and monoamine oxidase activities as related to the monoamine stores. J. Neurochem. 13, 597–605 (1969)
Levitt, M., Gibb, J. W., Daly, J. W., Lipton, M., Udenfriend, S.: A new class of tyrosine hydroxylase inhibitors and a simple assay of inhibition in vivo. Biochem. Pharmacol. 16, 1313–1321 (1967)
Lowry, O. H., Rosebrough, N. J., Farr, A. L., Randall, R. J.: Protein measurement with the Folin phenol reagent. J. biol. Chem. 193, 265–275 (1951)
Molinoff, P. B., Axelrod, J.: Biochemistry of catecholamines. Ann. Rev. Biochem. 40, 465–500 (1971)
Molinoff, P. B., Brimijoin, S., Axelrod, J.: Induction of dopamine β-hydroxylase in rat hearts and sympathetic ganglia. J. Pharmacol. exp. Ther. 182, 116–129 (1972)
Molinoff, P. B., Brimijoin, S., Weinshilboum, R., Axelrod, J.: Neurally mediated increase in dopamine β-hydroxylase activity. Proc. nat. Acad. Sci. (Wash.) 66, 453–458 (1970)
Mueller, R. A., Thoenen, H., Axelrod, J.: Increase in tyrosine hydroxylase activity after reserpine administration. J. Pharmacol. exp. Ther. 169, 74–79 (1969a)
Mueller, R. A., Thoenen, H., Axelrod, J.: Inhibition of trans-synaptically increased tyrosine hydroxylase activity by cycloheximide and actinomycin D. Molec. Pharmacol. 5, 463–469 (1969b)
Mueller, R. A., Thoenen, H., Axelrod, J.: Inhibition of neuronally induced tyrosine hydroxylase by nicotinic receptor blockade. Europ. J. Pharmacol. 10, 51–56 (1970)
Oesch, F., Otten, U., Thoenen, H.: Relationship between the rate of axoplasmic transport and subcellular distribution of enzymes involved in the synthesis of norepinephrine. J. Neurochem. 20, 1691–1706 (1973)
Patrick, R. L., Kirshner, N.: Effect of stimulation on levels of tyrosine hydroxylase, dopamine β-hydroxylase and catecholamine in intact and denervated rat adrenal glands. Molec. Pharmacol. 7, 87–96 (1971)
Snedecor, G. W., Cochran, W. G.: Statistical methods. Ames: Iowa State University Press 1967
Snider, S. R., Carlsson, A.: The adrenal dopamine as an indicator of adrenal medullary hormone biosynthesis. Naunyn-Schmiedeberg's Arch. Pharmacol. 275, 347–357 (1972)
Thoenen, H.: Neuronally mediated enzyme induction in adrenergic neurons and adrenal chromaffin cells. Biochem. Soc. Symp. 36, 3–15 (1972)
Thoenen, H., Kettler, R., Burkard, W., Saner, A.: Neuronally mediated control of enzymes involved in the synthesis of norepinephrine: are they regulated as an operational unit? Naunyn-Schmiedebergs Arch. Pharmak. 270, 146–160 (1971)
Weiner, N., Cloutier, G., Bjur, R., Pfeffer, R. I.: Modification of norepinephrine synthesis in intact tissue by drugs and during short-term adrenergic nerve stimulation. Pharmacol. Rev. 24, 203–221 (1972)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Otten, U., Paravicini, U., Oesch, F. et al. Time requirement for the single steps of trans-synaptic induction of tyrosine hydroxylase in the peripheral sympathetic nervous system. Naunyn-Schmiedeberg's Arch. Pharmacol. 280, 117–127 (1973). https://doi.org/10.1007/BF00499173
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00499173