Summary
The regional brain kinetics following 5-hydroxy-L-(β-11 C)tryptophan and L-(β-11 C)DOPA intravenous injection was measured in twelve Rhesus monkeys using positron emission tomography (PET). The radiolabelled compounds were also injected together with various doses of unlabelled 5-hydroxy-L-tryptophan or L-DOPA. The radioactivity accumulated in the striatal region and the rate of increased utilization with time was calculated using a graphical method with back of the brain as a reference region. The rate constants for decarboxylation were 0.0070 ± 0.0007 (S. D) and 0.0121±0.0010min−1 for 5-hydroxy-L-(β-11C)tryptophan and L-(β-11 C)DOPA, respectively. After concomitant injection with unlabelled 5-hydroxy-L-tryptophan, the rate constant of 5-hydroxy-L-(β-11 C)tryptophan decreased dose-dependently and a 50 percent reduction was seen with a dose of about 4mg/kg of unlabelled compound. A decreased utilization rate of L-(β-11 C)DOPA was seen only after simultaneous injection of 30 mg/kg of either L-DOPA or 5-hydroxy-L-tryptophan. This capacity limitation was most likely interpreted as different affinity of the striatal aromatic amino acid decarboxylase for L-DOPA and 5-hydroxy-L-tryptophan, respectively.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Bjurling P, Antoni G, Watanabe Y, Långström B (1990a) Enzymatic syntheses of carboxy-11 C-labelled L-tyrosine, L-dopa, L-tryptophan and 5-hydroxy-L-tryptophan. Acta Chem Scand 44: 178–182
Bjurling P, Watanabe Y, Oka S, Nagasawa T, Yamada H, Långström B (1990b) Multienzymatic synthesis of 11 C-labelled L-tyrosine and L-dopa. Acta Chem Scand 44: 183–188
Christenson JG, Dairman W, Udenfriend S (1970) Preparation and properties of a homogenous aromatic L-amino acid decarboxylase from hog kidney. Arch Biochem Biophys 141: 356–361
Christenson JG, Dairman W, Udenfriend S (1972) On the identity of DOPA decarboxylase and 5-hydroxytryptophan decarboxylase. Proc Natl Acad Sci USA 69: 343–347
Gjedde A, Reith J, Dyve S, Léger G, Guttman M, Diksic M, Evans A, Kuwabara H (1991) Dopa decarboxylase activity of the living human brain. Proc Natl Acad Sci 88: 2721–2725
Hartvig P, Lindner KJ, Tedroff J, Andersson Y, Bjurling P, Långström B (1992) Brain kinetics of 11 C-labelled L-tryptophan and 5-hydroxy-L-tryptophan in the Rhesus monkey: a study using positron emission tomography. J Neural Transm 88: 1–10
Holte S, Eriksson L, Dahlbom M (1989) A preliminary evaluation of the Scanditronix PC 2048-15 B brain scanner. Eur J Nucl Med 15: 719–721
Holtz P (1939) Dopadecarboxylase. Naturwissenschaften 27: 724–725
Ichiyama A, Nakamura S, Nishizuka Y, Hayashi O (1968) Tryptophan-5-hydroxylase in human brain. Adv Pharmacol 6A: 5–17
Kaufman S (1982) Properties of the pterin-dependent aromatic amino acid hydroxylases. In: Wolstenholme GEW, Fitzsimmons DW (eds) Aromatic amino acids in the brain. Ciba Foundation Symposium 22. Elsevier Science Publishers, Amsterdam, pp 85–108
Korf J, Reiffers S, Beerling-van der Holen HD, Lakke JPWF, Paans AMJ, Vaalburg W, Woldring MG (1978) Rapid decarboxylation of carbon-11 labelled LD-DOPA in the brain: a potential approach to external detection of nervous structures. Brain Res 145: 59–67
Koshimura K, Miwa S, Lee K, Fujiwara M, Watanabe Y (1990) Enhancement of dopamine release in vivo from the rat striatum by dialytic perfusion of 6R-L-erythro-5,6,7, 8-tetrahydrobiopterin. J Neurochem 54: 1391–1397
Litton J, Bergström M, Eriksson L, Bohm C, Blomqvist G, Kesselberg M (1984) Performance study of the PC-384 positron camera system for emission tomography of the brain. J Comput Assist Tomogr 8: 74–87
Lovenberg W, Weissbach H, Udenfriend S (1962) Aromatic L-amino acid decarboxylase. J Biol Chem 237: 89–93
Miwa S, Watanabe Y, Hayashi O (1985) 6R-L-Erythro-5,6,7,8-tetrahydrobiopterin as a regulator of dopamine and serotonin biosynthesis in the rat brain. Arch Biochem Biophys 239: 234–241
Miwa S, Gillberg P, Bjurling P, Yumoto N, Odano I, Watanabe Y, Långström B (1992) Assessment of dopamine and its metabolites in the intracellular and extracellular compartments of the rat striatum after peripheral administration of L-(11 C)DOPA. Brain Res 578: 122–128
van Praag HM, de Haan S (1980) Depression vulnerability and 5-hydroxytryptophan prophylaxis. Psychiatry Res 3: 75–83
Reibring L, Ågren H, Hartvig P, Tedroff J, Lundqvist H, Bjurling P, Kihlberg T, Långström B (1992) Uptake and utilization of (beta-11 C)5-hydroxytryptophan in human brain studied by positron emission tomography. Psychiatry Res: Neuroimaging 45: 215–225
Rosetti ZL, Silvia CP, Krajnc D, Neff NH, Hadjiconstantinou M (1989) Modulation of aromatic amino acid decarboxylase via a-2-adrenoceptors. J Neurochem 52: 647–652
Rosetti ZL, Silvia CP, Krajnc D, Neff NH, Hadjiconstantinou M (1990) Aromatic Lamino acid decarboxylase is modulated by D1 dopamine receptors in rat retina. J Neurochem 54: 787–791
Rota Kops E, Herzog H, Schmid A, Holte S, Feinendegen L (1990) Performance characteristic of an eight ring whole body PET scanner. J Comput Assist Tomogr 14: 437–445
Sims KL, Davies GA, Bloom FE (1973) Activities of 3,4-dihydroxy-L-phenyl-alanine and 5-hydroxy-L-tryptophan decarboxylases in rat brain: assays characteristics and distribution. Exp Brain Res 59: 575–581
Siow YL, Dakshinamurti K (1990) Neuronal DOPA decarboxylase. Ann NY Acad Sci 585: 173–188
Sourkes TL (1977) Enzymology of aromatic amino acid decarboxylase In: Usdin E, Weiner N, Youdim MBH (eds) Structure and function of monoamine enzymes. Marcel Dekker, New York, pp 477–496
Tedroff J, Aquilonius SM, Hartvig P, Bjurling P, Långström B (1992a) Estimation of regional cerebral utilization of (11 C)-L-3,4-dihydroxy-phenylalanine (DOPA) in the primate by positron emission tomography. Acta Neurol Scand 85: 166–173
Tedroff J, Aquilonius SM, Hartvig P, Bredberg E, Bjurling P, Långström B (1992b) Cerebral uptake and utilization of (11 C)-L-DOPA in Parkinson's disease measured by positron emission tomography-relations to motor response. Acta Neurol Scand 85: 95–102
Watanabe Y, Hartvig P, Tedroff J, Bjurling P, Miwa S, Hayashi T, Noguchi T, Långström B (1991) Elevation of dopamine turnover in vivo by peripheral administration of 6 Rtetrahydrobiopterin in monkey striatum. In: Blau N, et al (eds) Pteridine and related biologic amines in neuropsychiatry, pediatrics and immunology. Lakeshore Publishing Company, pp 353–362
Zhu MY, Juorio AV, Paterson IA, Boulton AA (1992) Regulation of aromatic L-amino acid decarboxylase by dopamine receptors in the rat brain. J Neurochem 58: 636–641
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hartvig, P., Tedroff, J., Lindner, K.J. et al. Positron emission tomographic studies on aromatic L-amino acid decarboxylase activity in vivo for L-dopa and 5-hydroxy-L-tryptophan in the monkey brain. J. Neural Transmission 94, 127–135 (1993). https://doi.org/10.1007/BF01245006
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01245006