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THE LONG‐TERM REGULATION OF TYROSINE HYDROXYLASE ACTIVITY IN CULTURED SYMPATHETIC GANGLIA: ROLE OF GANGLIONIC NORADRENALINE CONTENT
Author(s) -
MACKAY A.V.P.
Publication year - 1974
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1974.tb09669.x
Subject(s) - medicine , endocrinology , cycloheximide , depolarization , ouabain , tyrosine hydroxylase , tyrosine 3 monooxygenase , reserpine , superior cervical ganglion , extracellular , biology , chemistry , sodium , biochemistry , dopamine , protein biosynthesis , organic chemistry
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.