THE LONG-TERM REGULATION OF TYROSINE HYDROXYLASE ACTIVITY IN CULTURED SYMPATHETIC GANGLIA: ROLE OF GANGLIONIC NORADRENALINE CONTENT

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Abstract
1 An organ culture system is described for the in vitro maintenance of superior cervical sympathetic ganglia taken from mice of any age. The relation of tyrosine hydroxylase (T-OH) activity to ganglionic noradrenaline (NA) content has been investigated under various culture conditions. 2 Depolarizing stimuli such as raised extracellular potassium and ouabain evoked increases of approximately 70% in the T-OH activity of cultured ganglia over a 48 h period. Exposure to a high concentration of potassium (high K+) for 30 min at the start of a 48 h culture was sufficient to elicit significant increases in T-OH activity. 3 Depolarization-induced rises in T-OH activity were observed after culture in the presence or absence of nerve growth factor. 4 The NA content of ganglia, cultured for 48 h in the presence of high K+, ouabain, reserpine, clorgyline and α-methyl-p-tyrosine, showed no constant relation to their T-OH activity. 5 Dibutyryl cyclic adenosine 3′-5′-monophosphate (dibutyryl cyclic AMP) mimicked high K+ in its effect on ganglionic T-OH activity and NA content. Theophylline enhanced the potassium effects. 6 Rises in the T-OH activity of ganglia cultured in the presence of high K+ and dibutyryl cyclic AMP were abolished if the protein synthesis inhibitors cycloheximide or actinomycin D were present in the culture medium. 7 It is concluded that the link between prolonged depolarization and rises in T-OH activity does not seem to depend upon changes in ganglionic NA content. In the intact animals, trans-synaptic modulation may take the form of a depolarization-induced rise in the cyclic AMP content of sympathetic ganglionic neurones leading to nuclear mediated synthesis of T-OH.