Comparison of tyrosine hydroxylase and choline acetyltransferase activity in response to sympathetic nervous system activation.

Choline acetyltransferase and tyrosine hydroxylase serve as enzyme markers for preganglionic and postganglionic sympathetic nerves, respectively. There is abundant evidence that experimental conditions which increase the activity of the peripheral sympathetic nervous system produce an increase in the activity of neuronal tyrosine hydroxylase and dopamine fl-hydroxylase 11. The activity of these enzymes serve as indices of sympathetic neural activity. It is not known, however, if choline acetyltrans-ferase activity also serves as a reliable index of neural activity. Initial studies by Mueller and co-workers showed that 6-hydroxydopamine t4 and reserpine injection 15 increased the activity of tyrosine hydroxylase within the terminals of adrenergic neurons and in the adrenal medulla. Molinoff et al. 12 demonstrated a neurally mediated increase in dopamine-fl-hydroxylase. Subsequent studies employing a variety of conditions such as cold 1,2a, immobilization 8, ampheta-mine 10, insulin 25, phenoxybenzamine a, swimming 24 and hypothalamic stimulation is also increase tyrosine hydroxylase activity in the peripheral sympathetic system and adrenals. Since the increase in tyrosine hydroxylase activity is blocked by RNA and protein synthesis inhibitors 16, it was suggested that there is an increase in enzyme synthesis. Using immunoprecipitation, Chuang and Costa 1 showed that there is an increase in enzyme protein in response to cold stress in rats. In addition to the increased activity requiring protein synthesis, there may be a short-term regulation of activity, associated with protein phosphorylation 7,~ and changes in apparent sub-strate affinities 26. In contrast to tyrosine hydroxylase, relatively few studies have been performed on the regulation of choline acetyltransferase activity in the sympathetic nervous system. Oesch has, for example, examined the effect of reserpine injection into rats on the activity of choline acetyltransferase in stellate and superior cervical ganglia and in the adrenal medulla 17. He reported that the activity increases in response to reserpine treatment. As reported in preliminary form 2~, we find that tyrosine hydroxylase activity is more responsive than choline acetyltransferase and that large, perhaps supraphy-siologic, stimuli are necessary to increase activity.