Further characterization of the tyrosine hydroxylase induction elicited by reserpine in the rat locus coeruleus and adrenals.
This study shows that reserpine causes a long lasting increase in the amount of protein and activity of tyrosine hydroxylase (TH) in central noradrenergic neurons of the locus coeruleus (LC) and in peripheral cells of the adrenal gland. In these structures, the drug effect appears to be reversible (maximum at day 2-4 after injection) and is entirely dose-dependent. Variations in TH activity were measured both in vitro in optimal enzymatic conditions and in vivo. Reserpine did not modify the ratio between activities measured in vivo and in vitro. But it decreased the specific activity of the enzyme as measured in homogenates of LC. The reversibility of the reserpine effect on all parameters studied appeared faster in adrenal than in central LC neurons. Reserpine did not change the activity and amount of TH in the region of the substantia nigra where dopaminergic neurons are located, except at a high dose (10 mg/kg): a significant elevation (+36%) of the TH protein amount was then observed 2 days after treatment. Moreover, reserpine did not influence the amount of neuron specific enolase in the LC region at a time when maximal effect was observed for TH, thus showing the biochemical specificity of this regulation. Concomitant injection of clonidine at two doses 30 min before (100?g/kg) and 3 h after (50?g/kg) reserpine administration did not affect the induction by reserpine alone. Thus, stimulation of LC noradrenergic cell firing resulting from reserpine administration is probably of negligible importance in the genesis of TH induction by this drug.
Richard
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F
INSERM U 171, CNRS UA 1195, Centre Hospitalier Lyon-Sud, Pavillon 4H, Chemin du Grand Revoyet, 69310 Pierre Benite, France.
Labatut
R
R
Weissmann
D
D
Scarna
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H
Buda
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M
Pujol
J F
JF