Effect of Reserpine on Monoamine Synthesis and on Apparent Dopaminergic Receptor Sensitivity in Rat Brain
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There seems to be general agreement that the monoamine-depleting action of reserpine is due to blockade of the uptake mechanisms located in the intracellular storage organelles, generally called “granules” or “synaptic vesicles” (see Carlsson, 1965). Although the monoamine-synthesizing enzymes are not primarily involved, several secondary actions on the activities of these enzymes have been demonstrated or proposed. Dopamine-β-hydroxylase is located in the storage granules, and the blocking action of reserpine on their uptake mechanism may lead to reduced availability of the substrate dopamine (Rutledge and Weiner, 1967). As to the first steps in the synthesis of monoamines, i.e., the hydroxylation of tyrosine and tryptophan, the action of reserpine on the storage mechanism appears to cause rather complex secondary changes in the activity of the enzymes involved. Sustained increases in 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid levels in brain after reserpine treatment, outlasting the initial phase of monoamine net release, may indicate increased rates of monoamine synthesis, even though alternative explanations cannot be excluded (Andén et al, 1963, 1964).
KeywordsTyrosine Hydroxylase Tryptophan Hydroxylase Brain Part Tryptophan Level Tyrosine Hydroxylase Activity
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- Carlsson, A., 1965, Drugs which block the storage of 5-hydroxytryptamine and related amines, in: Handbuch der experimentellen Pharmakologie, Vol. XíX (V. Erspamer, ed.), pp. 529–592, Springer-Verlag, Berlin and Heidelberg.Google Scholar
- Carlsson, A., 1975, Receptor-mediated control of dopamine metabolism, in: Pre-and Postsyn-aptic Receptors (E. Usdin and W. E. Bunney, eds.), pp. 49–65, Marcel Dekker, New York.Google Scholar
- Carlsson, A., Kehr, W., and Lindqvist, M., 1976, Agonist-antagonist interaction on dopamine receptors in brain, as reflected in the rates of tyrosine and tryptophan hydroxylation, in: Advances in Parkinsonism: Biochemistry, Physiology, Treatment (W. Birkmayer and O. Hornykiewicz, eds.), Editiones Roche, Basle, pp. 71–81.Google Scholar
- Kehr, W., Carlsson, A., and Lindqvist, M., 1975, Biochemical aspects of dopamine agonists, in: Advances in Neurology, Vol. 9 (D. B. Calne, T. N. Chase, and A. Barbeau, eds.), pp. 185–195, Raven Press, New York.Google Scholar
- Tozer, T. N., Neff, N. H., and Brodie, B. B., 1966, Application of steady state kinetics to the synthesis rate and turnover time of serotonin in the brain of normal and reserpine-treated rats, J. Pharmacol. Exp. Ther. 153:177.Google Scholar