Summary
Using a microdialysis technique, the rat striatum was perfused with NSD-1015, an inhibitor of aromatic L-amino acid decarboxylase, and the amount of L-3,4-dihydroxyphenylalanine (L-DOPA) and 5-hydroxytrytophan (5-HTP) accumulating in dialysate was measured as an index of in vivo activities of tyrosine hydroxylase and tryptophan hydroxylase. NSD-1015 increased the concentration of L-DOPA much higher than that of 5-HTP in a dose-related manner (1–100 μmol/L). In order to examine the relationship between dopaminergic and serotonergic neurons in the striatum, either 5-HTP or L-DOPA was injected intraperitoneally to rats pretreated with benserazide, an inhibitor of peripheral decarboxylase. 5-HTP administration increased 5-HTP, but decreased L-DOPA in a dose-dependent manner. Conversely, 5-HTP concentration decreased in an association with the increased content of L-DOPA following L-DOPA administration. The decrease of 5-HTP caused by L-DOPA administration was not as remarkable as that of L-DOPA by 5-HTP injection. These results suggest that L-DOPA and 5-HTP, the precursor amino acids for catecholamines and indoleamines, could affect mutually each other neuronal activity through the inhibition of their rate-limiting enzymes.
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Abbreviations
- AADC :
-
aromatic L-aminoacid decarboxylase
- ANOVA :
-
analysis of variance
- DA :
-
dopamine
- DOPAC :
-
3,4-dihydroxyphenylacetic acid
- ECD :
-
electrochemicaldetection
- 5-HIAA :
-
5-hydroxyindoleacetic acid
- HPLC :
-
high performance liquid chromatography
- 5-HT :
-
5-hydroxytryptamine (serotonin)
- 5-HTP :
-
5-hydroxytryptophan
- HVA :
-
homovanillic acid
- Km :
-
Michaelis constant
- L-DOPA :
-
L-3,4-dihydroxyphenylalanine
- (6 R)BH4 :
-
(6R)-L-erythro-tetrahydrobiopterin
- TH :
-
tyrosine hydroxylase
- TRH :
-
tryptophan hydroxylase
- TRP :
-
tryptophan
- TYR :
-
tyrosine
References
Abercrombie ED, Bonatz AE, Zigmond MJ (1992) Effects of L-DOPA on extracellular dopamine in striatum of normal and 6-hydroxydopamine-treated rats. Brain Res 525: 36–44
Baumann P (1985) Transport systems and enzymes involved in the metamorphosis of tryptophan into serotonin. Pharmacopsychiatry 18: 188–192
Bigelow LB, Walls P, Gillin JC, Wyatt RJ (1979) Clinical effects of L-5-hydroxytryptophan administration in chronic schizophrenic patients. Biol Psychiatry 14: 53–67
Brock JW, Ng JP, Justice Jr JB (1990) Effect of chronic cocaine on dopamine synthesis in the nucleus accumbens as determined by microdialysis perfusion with NSD-1015. Neurosci Lett 117: 234–239
Cooper JR, Bloom FE, Roth RH (1991) The biochemical basis of neuropharmacology, 6th ed. Oxford University Press, New York, pp 285–367
Goldstein M, Frenkel R (1971) Inhibition of serotonin synthesis by dopa and other catechols. Nature New Biol 233: 179–180
Goodwin FK, Dunner DL, Gershon ES (1971) Effect of L-DOPA treatment on brain serotonin metabolism in depressed patients. Life Sci 10: 751–759
Ichinose H, Ozaki N, Nakahara D, Naoi M, Wakabayashi K, Sugimura T, Nagatsu T (1988) Effects of heterocyclic amines in food on dopamine metabolism in nigro-striatal dopaminergic neurons. Biochem Pharmacol 37: 3289–3295
Levine RA, Miller LP, Lovenberg W (1981) Tetrahydrobiopterin in striatum: localization in dopamine nerve terminals and role in catecholamine synthesis. Science 214: 919–921
Maruyama W, Minami M, Ota A, Takahashi A, Nagatsu T, Naoi M (1991) Reduction of enzymatic activity of tyrosine hydroxylase by a heterocyclic amine, 3-amino-1,4-dimethyl-5H-pyrido (4,3-b) indole (Trp-P-1), was due to reduced affinity to a cofactor biopterin. Neurosci Lett 125: 85–88
Maruyama W, Naoi M, Takahashi A, Watanabe H, Konagaya Y, Mokuno K, Hasegawa S, Nakahara D (1992) The mechanism of pertubation in monoamine metabolism by L-DOPA therapy; in vivo and in vitro studies. J Neural Transm 90: 183–197
McGeer EG, McGeer PL (1967) In vitro screen of inhibitors of rat brain tyrosine hydroxylase. Can J Biochem 45: 115–131
Minami M, Takahashi T, Maruyama W, Takahashi A, Nagatsu T, Naoi M (1991) Allosteric effect of tetrahydrobiopterin cofactors on tyrosine hydroxylase activity. Life Sci 50: 15–20
Minami M, Takahashi T, Maruyama W, Takahashi A, Dostert P, Nagatsu T, Naoi M (1992) Inhibition of tyrosine hydroxylase by R and S enantiomers of salsolinols, 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline. J Neurochem 58: 2097–2101
Nakahara D, Ozaki N, Nagatsu T (1989) A removable brain microdialysis probe unit for in vivo monitoring of neurochemical activity. Biogenic Amines 6: 559–564
Naoi M, Takahashi T, Ichinose H, Wakabayashi K, Sugimura T, Nagatsu T (1988) Reduction of enzyme activity of tyrosine hydroxylase and aromatic L-amino acid decarboxylase in clonal pheochromocytoma PC 12h cells by carcinogenic amines. Biochem Biophys Res Commun 157: 494–499
Naoi M, Hosoda S, Ota M, Takahashi T, Nagatsu T (1991a) Inhibition of tryptophan hydroxylase by food-derived carcinogenic heterocyclic amines, 3-amino-1-methyl-5H-pyrido[4,3-b]indole and 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole. Biochem Pharmacol 41: 199–203
Naoi M, Niwa T, Yoshida M, Nagatsu T (1991b) Tetrahydroisoquinoline and its derivatives: the occurrence and the metabolism in the brain, and the effects on catecholamine metabolism. In: Nagatsu T, Narabayashi H, Yoshida M (eds) Parkinson's disease. From clinical aspects to molecular basis. Springer, Wien New York, pp 73–84 (Key Topics in Brain Research)
Nisenbaum LK, Abercrombie ED (1992) Enhanced tyrosine hydroxylation in hippocampus of chronically stressed rats upon exposure to a novel Stressor. J Neurochem 58: 276–281
Ota M, Dostert P, Hamanaka T, Nagatsu T, Naoi M (1992) Inhibition of tryptophan hydroxylase by (R)- and (S)-1-methyl-6,7-dihydroxy-1,2,3,4-terahydroisoquinolines (salsolinols). Neuropharmacology 31: 337–341
Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates, 2nd ed. Academic Press, Sydney
Roberge AG, Poirier LJ (1973) Effect of chronically administered L-DOPA on DOPA/ 5HTP decarboxylase and tyrosine and tryptophan hydroxylases in cat brain. J Neural Transm 34: 171–185
Sumi C, Ichinose H, Nagatsu T (1990) Characterization of recombinant human aromatic L-amino acid decarboylase expressed in COS cells. J Neurochem 55: 1075–1078
Westerink BHC, De Vries JB (1991) Effect of precursor loading on the synthesis rate and release of dopamine and serotonin in the striatum: a microdialysis study in conscious rats. J Neurochem 56: 228–233
Westerink BHC, De Vries JB, Duran R (1990) Use of microdialysis for monitoring tyrosine hydroxylase activity in the brain of conscious rats. J Neurochem 54: 381–387
Zhelyaskov DK, Levitt M, Udenfriend S (1968) Tryptophan derivatives as inhibitors of tyrosine hydroxylase in vivo and in vitro. Mol Pharmacol 4: 445–451
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Hashiguti, H., Nakahara, D., Maruyama, W. et al. Simultaneous determination of in vivo hydroxylation of tyrosine and tryptophan in rat striatum by microdialysis-HPLC: relationship between dopamine and serotonin biosynthesis. J. Neural Transmission 93, 213–223 (1993). https://doi.org/10.1007/BF01244998
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DOI: https://doi.org/10.1007/BF01244998