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Abstract
This thesis describes studies done on both the long-term and short-term regulation of tyrosine hydroxylase (TH) activity by preganglionic nerve activity, glucocorticoids, cholinergic agonists and peptides in the rat superior cervical ganglion (SCG) in vitro.
Preganglionic nerve stimulation in vitro at 10 Hz for 30 min produces an increase in TH activity in ganglia maintained in organ culture. This increase in TH activity occurs with a lag period of at least 12 h, and elevated enzyme activity is maintained for 2 days. The magnitude of the increase in TH activity depends on the frequency and duration of stimulation. Nicotinic receptors play an important role in mediating this trans-synaptic regulation of TH activity. The effect of brief periods of stimulation is potentiated by dexamethasone.
Incubation of ganglia with cholinergic agonists produce an acute increase in TH activity within minutes. The effect of carbachol on TH activity is mediated by both nicotinic and muscarinic receptors. Dimethylphenylpiperazinium (DMPP) and bethanechol also produce acute increases in TH activity. The effect of DMPP, but not of bethanechol, can be inhibited by substance P.
Preganglionic nerve stimulation in vitro at 10 Hz also leads to an acute increase in TH activity within minutes. This increase appears to be mediated in part by acetylcholine and in part by a non-cholinergic transmitter. The relative magnitude of the increases in TH activity produced by cholinergic and non-cholinergic mechanisms depends on the stimulation parameters used. A discontinuous pattern of stimulation produces a rapid increase in TH activity that appears to be entirely non-cholinergic. Elevation of the K('+) concentration in the medium also increases TH activity. This effect of K('+) may be mediated both by the release of a non-cholinergic transmitter from the preganglionic nerve terminals and by direct depolarization of ganglionic nerve terminals and by direct depolarization of ganglionic neurons.
As a first step in an attempt to identify the transmitter responsible for the non-cholinergic effect of preganglionic nerve stimulation, seventeen neuropeptides were examined for their ability to increase TH activity acutely in the SCG. Of the peptides studied, secretin, VIP and PHI are effective. Both VIP and PHI are about 2 orders of magnitude less potent than secretin. These peptides appear to act directly on ganglionic neurons to increase TH activity. The effects of secretin and VIP can be potentiated by the addition of carbachol.
