Molecular Pharmacology, Vol 12, 353-361, Copyright © 1976 by the American Society for Pharmacology and Experimental Therapeutics

Selective Induction of Tyrosine Hydroxylase and Dopamine -Hydroxylase in Sympathetic Ganglia in Organ Culture: Role of Glucocorticoids as Modulators

¹ Department of Pharmacology, Biocenter of the University, Basel, Switzerland

In organ cultures of rat sympathetic ganglia dexamethasone enhanced the synthesis of tyrosine hydroxylase and dopamine -hydroxylase in a strictly dose-dependent manner. The maximal effect (tyrosine hydroxylase, +64%; dopamine -hydroxylase, +47%) was achieved at 0.1 µM, and at 100 µM control levels were approached again. In contrast, the smaller effect on dopa decarboxylase (+24%) was virtually the same over the concentration range from 10 nM to 1 mM. For all the enzymes studied a 4-hr exposure of the ganglia to glucocorticoids was sufficient to produce a maximal effect after 48 hr. The glucocorticoid-mediated induction of tyrosine hydroxylase and dopamine -hydroxylase was dependent on the presence of intact preganglionic cholinergic nerves. In decentralized ganglia the increase in tyrosine hydroxylase was reduced to +22%, and that of dopamine -hydroxylase, to +4%. The increase in dopa decarboxylase remained unchanged. The addition of the ganglionic blocking agent chlorisondamine (10 µM) had the same effect as decentralization. In organ cultures originating from adrenalectomized animals carbamylcholine (100 µM) still produced a marked increase in tyrosine hydroxylase and dopamine -hydroxylase. It is concluded that glucocorticoids exert a dual effect on sympathetic ganglia: (a) a strictly concentration-dependent induction of tyrosine hydroxylase and dopamine -hydroxylase, which depends on the presence of intact preganglionic cholinergic nerves, and (b) a nonspecific general effect on protein synthesis, which is not dependent on intact preganglionic nerves and which is reflected by a small increase of all enzymes studied. Since specific induction of tyrosine hydroxylase and dopamine -hydroxylase by carbamylcholine is still possible in ganglia from adrenalectomized animals, the synthesis of these two enzymes seems to be regulated primarily by the activity of the preganglionic nerves, with glucocorticoids playing a modulatory role.

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ACKNOWLEDGMENTS The authors wish to thank Mrs. N. Scott-Lindsay for her excellent technical assistance, and Miss V. Forster for her help in preparation of the manuscript.

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