Tryptophan Hydroxylation: Measurement in Pineal Gland, Brainstem, and Carcinoid Tumor

Lovenberg, Walter; Jéquier, E; Sjoerdsma, Albert

doi:10.1126/science.155.3759.217

Cited by 445 publications

(152 citation statements)

References 10 publications

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“…The effects of galanin on TrpH, the rate-limiting enzyme in the biosynthesis of 5-HT (Lovenberg et al 1967) likely that the inhibition of TrpH enzyme activity by galanin is indirectly mediated by the inhibition of the raphe cell firing similarly to 5-HT 1A receptor agonists (Invernizzi et al 1991).…”

Section: Discussionmentioning

confidence: 99%

Galanin Is a Potent In Vivo Modulator of Mesencephalic Serotonergic Neurotransmission

Kehr

Yoshitake

Wang

et al. 2002

Neuropsychopharmacology

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Section: Discussionmentioning

confidence: 99%

Galanin Is a Potent In Vivo Modulator of Mesencephalic Serotonergic Neurotransmission

Kehr

Yoshitake

Wang

et al. 2002

Neuropsychopharmacology

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“…b Lovenberg et al (1967). c Tappaz and Pujol (1980), Chaouloff et al (1985), and Neckers and Meek (1976).…”

Section: Resultsmentioning

confidence: 99%

A New Method to Measure Brain Serotonin Synthesis in vivo. I. Theory and Basic Data for a Biological Model

Dikšić

Saijo

Sourkes

et al. 1990

J Cereb Blood Flow Metab

168

137

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Summary:We describe here an autoradiographic method to measure the in vivo rate of serotonin synthesis in rat brain. The method is based on the use of the L-tryptophan analogue a-methyl-L-tryptophan (a-MTrp), which is con verted in vivo into a-methyl serotonin (a-M5HT). Since a-M5HT is not a substrate for monoamine oxidase, it is accumulated in the brain tissue. Data are presented to confirm time-dependent conversion of a-MTrp into a-M5HT in the dorsal raphe nucleus and also in the pineal body, an organ outside the blood-brain barrier. It has also Several methods have been proposed to measure serotonin synthesis in the brain of laboratory ani mals (for review, see Haber et aI., 198 1; Korf, 1985). Two approaches have been used, i.e., steady state and non-steady state. The rate of serotonin synthesis has usually been estimated on the basis of changes in the concentration of tryptophan metab olites [5-hydroxytryptophan, 5-hydroxytryptamine, or 5-hydroxyindoleacetic acid (5HIAA)] after some kind of pharmacological manipulation. Serotonin (5-hydroxytryptamine) is synthesized from L tryptophan in a two-step enzymatic process. The first step, hydroxylation of L-tryptophan with tryp tophan 5-hydroxylase (EC 1. 14. 16.4), requiring tet rahydrobiopterin as a co-factor and molecular oxy-

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“…[1][2][3] A second TPH isoform identified by Walther et al, 4 in 2003, is termed TPH2, while the original TPH isoform is now termed TPH1. TPH2 is the predominant central nervous system (CNS) isoform in all species examined thus far, with TPH2 messenger RNA expressed throughout the raphe nuclei.…”

Section: Introductionmentioning

confidence: 99%

Glucocorticoid modulation of tryptophan hydroxylase-2 protein in raphe nuclei and 5-hydroxytryptophan concentrations in frontal cortex of C57/Bl6 mice

et al. 2007

Mol Psychiatry

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Considerable attention has focused on regulation of central tryptophan hydroxylase (TPH) activity and protein expression. At the time of these earlier studies, it was thought that there was a single central TPH isoform. However, with the recent identification of TPH2, it becomes important to distinguish between regulatory effects on the protein expression and activity of the two isoforms. We have generated a TPH2-specific polyclonal antiserum (TPH2-6361) to study regulation of TPH2 at the protein level and to examine the distribution of TPH2 expression in rodent and human brain. TPH2 immunoreactivity (IR) was detected throughout the raphe nuclei, in lateral hypothalamic nuclei and in the pineal body of rodent and human brain. In addition, a prominent TPH2-IR fiber network was found in the human median eminence. We recently reported that glucocorticoid treatment of C57/Bl6 mice for 4 days markedly decreased TPH2 messenger RNA levels in the raphe nuclei, whereas TPH1 mRNA was unaffected. The glucocorticoid-elicited inhibition of TPH2 gene expression was blocked by co-administration of the glucocorticoid receptor antagonist mifepristone (RU-486). Using TPH2-6361, we have extended these findings to show a dose-dependent decrease in raphe TPH2 protein levels in response to 4 days of treatment with dexamethasone; this effect was blocked by co-administration of mifepristone. Moreover, the glucocorticoid-elicited inhibition of TPH2 was functionally significant: serotonin synthesis was significantly reduced in the frontal cortex of glucocorticoid-treated mice, an effect that was blocked by mifepristone coadministration. This study provides further evidence for the glucocorticoid regulation of serotonin biosynthesis via inhibition of TPH2 expression, and suggest that elevated glucocorticoid levels may be relevant to the etiology of psychiatric diseases, such as depression, where hypothalamic-pituitary-adrenal axis dysregulation has been documented.

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Tryptophan Hydroxylation: Measurement in Pineal Gland, Brainstem, and Carcinoid Tumor

Cited by 445 publications

References 10 publications

Galanin Is a Potent In Vivo Modulator of Mesencephalic Serotonergic Neurotransmission

Galanin Is a Potent In Vivo Modulator of Mesencephalic Serotonergic Neurotransmission

A New Method to Measure Brain Serotonin Synthesis in vivo. I. Theory and Basic Data for a Biological Model

Glucocorticoid modulation of tryptophan hydroxylase-2 protein in raphe nuclei and 5-hydroxytryptophan concentrations in frontal cortex of C57/Bl6 mice

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