Summary
The investigation was carried out in order to establish the origin of 5-hydroxytryptophan (5-HTP) accumulating in the brain following treatment with he decarboxylase inhibitor Ro 4-4602 [N-(DL seryl)-N1-(2,3,4-trihydroxybenzyl) hydrazine].
In biochemical studies the distribution of 5-HTP in the brain of rats treated with Ro 4-4602 was similar to the normal distribution of 5-hydroxytryptamine (5-HT). In contrast the 5-HTP accumulating after i.p. injection of this compound was evenly distributed in different parts of the brain.
In histochemical studies performed on reserpine-treated rats specific fluorescence, apparently derived from accumulating 5-HTP and dopa, could be demonstrated in 5-HT- and dopamine-carrying nerve cell bodies and terminals following treatment with Ro 4-4602.
Taken together, the available biochemical and histochemical studies indicate that the 5-hydroxytryptophan and dopa accumulating in the brain following decarboxylase inhibition are mainly or entirely formed by the aromatic amino acid hydroxylases of central 5-HT- and catecholamine-carrying neurons, respectively.
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References
Andén, N.-E., Magnusson, T.: An improved method for the fluorimetric determination of 5-hydroxytryptamine in tissues. Acta physiol. scand.69, 87–94 (1967).
Ashcroft, G. W., Eccleston, D., Crawford, T. B. B.: 5-Hydroxyindole metabolism in rat brain. A study of intermediate metabolism using the technique of tryptophan loading. - I. Methods. J. Neurochem.12, 483–492 (1965).
Atack, C. V., Magnusson, T.: Individual elution of noradrenaline (together with adrenaline), dopamine, 5-hydroxytryptamine and histamine from a single, strong cation exchange column, by means of mineral acid-organic solvent mixtures. J. Pharm. Pharmacol.22, 625–627 (1970).
Burkard, W. P., Gey, K. F., Pletscher, A.: Inhibition of decarboxylase of aromatic amino acids by 2,3,4-trihydroxybenzylhydrazine and its seryl derivative. Arch. Biochem.107, 187–196 (1964).
Carlsson, A., Falck, B., Hillarp, N.-Å.: Cellular localization of brain monoamines. Acta physiol. scand.56, Suppl. 196, 1–28 (1962).
—, Lindqvist, M.: Accumulation of 5-hydroxytryptophan in mouse brain after decarboxylase inhibition. J. Pharm. Pharmacol.22, 726–727 (1970).
Cegrell, L., Nordgren, L., Rosengren, A. M.: Effect of decarboxylase inhibition and neuroleptic drugs on the DOPA level in rat brain. Res. Comm. Chem. Path. Pharmacol.1, 479–484 (1970).
Dahlström, A., Fuxe, K.: Evidence for the existence of monoamine-containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurons. Acta physiol. scand.62, Suppl. 232, 1–55 (1964).
Falck, B., Hillarp, N.-Å., Thieme, G., Torp, A.: Fluorescence of catecholamines and related compounds condensed with formaldehyde. J. Histochem. Cytochem.10, 348–354 (1962).
Fuxe, K., Hökfelt, T., Ungerstedt, U.: Localization of indole alkylamines in the C.N.S. Advanc. Pharmacol.6 A, 235–251 (1968).
Hillarp, N.-Å., Fuxe, K., Dahlström, A.: Central monoamine neurons. In: Mechanisms of release of biogenic amines (eds. U.S. v. Euler, S. Rosell, and B. Uvnäs), pp. 34–58. Oxford: Pergamon Press 1966.
Ichiyama, A., Nakamura, S., Nishizuka, Y., Hayaishi, O.: Tryptophan-5-hydroxylase in mammalian brain. Advanc. Pharmacol.6 A, 5–17 (1968).
Jonsson, G.: Fluorescence methods for the histochemical demonstration of monoamines. VII. Fluorescence studies on biogenic monoamines and related compounds condensed with formaldehyde. Histochemie8, 288–296 (1967).
Lindqvist, M.: Quantitative estimation of 5-hydroxy-3-indole acetic acid and 5-hydroxytryptophan in brain following isolation by means of a strong cation exchange column. Acta pharmacol. (Kbh.)29, 303–313 (1971).
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Fellow of the Medical Research Council of Canada.
This study has been supported by grants (14X-715-06C; B71-14X-155-07C) from the Swedish Medical Research Council and by grants from “Ollie och Elof Ericssons Stiftelse” and “Magn. Bergvalls Stiftelse”. We thank Dr. A. Pletscher, Fa. I-Ioffmann-La Roche and Co., for a generous supply of Ro 4-4602.
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Bédard, P., Carlsson, A., Fuxe, K. et al. Origin of 5-hydroxytryptophan and L-dopa accumulating in brain following decarboxylase inhibition. Naunyn-Schmiedebergs Arch. Pharmak. 269, 1–6 (1971). https://doi.org/10.1007/BF01422011
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DOI: https://doi.org/10.1007/BF01422011