Variation of tryptophan-5-hydroxylase concentration in the rat raphe dorsalis nucleus afterp-chlorophenylalanine administration. I. A model to study the turnover of the enzymatic protein

Richard, Françoise; Sanne, Jean-Luc; Bourde, Odile; Weissmann, Dinah; Ehret, M.; Cash, Christopher D.; Maître, Michel; Pujol, Jean‐François

doi:10.1016/0006-8993(90)90006-w

Cited by 32 publications

(14 citation statements)

References 18 publications

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“…This is also in keeping with the suggestion that increases in TPH gene expression occur in the dorsal raphe nucleus (DR) following 5-HT depletion with fenfluramine, an anorexic agent that induces 5-HT release and blocks its reuptake from nerve terminals (Bendotti et al, 1993). Such treatment was accompanied by a concomitant recovery of TPH content, similar to what has been observed following PCPA administration (Park et al, 1994;Richard et al, 1990).…”

Section: Introductionsupporting

confidence: 85%

Origin of the serotonergic innervation to the rat dorsolateral hypothalamus: Retrograde transport of cholera toxin and upregulation of tryptophan hydroxylase mRNA expression following selective nerve terminals lesion

Ljubic‐Thibal

Morin

Dikšić

et al. 1999

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The regulation of serotonin synthesis was investigated in the serotonergic neurons, which provide afferents to the dorsolateral hypothalamus (DLH). The origin of the DLH projection neurons within the raphe nucleus was identified by retrograde transport of Cholera toxin (CTb) and their serotonergic nature confirmed by tryptophan hydroxylase (TPH) immunocytochemistry. Disruption of serotonin synthesis steady-state was induced unilaterally by a selective and local destruction of serotonergic nerve terminals with 5,7-dihydroxytryptamine (5,7-DHT), stereotaxically injected in the right DLH. The results show that most of the serotonergic dorsal raphe neurons projecting to the DLH have an ipsilateral localization within the lateral aspects of the nucleus. In rats with unilateral DLH lesion, a population of serotonergic cells within the raphe nucleus exhibited a clear increase in TPH mRNA. These cells were about five times more numerous in the ipsilateral as compared to the contralateral dorsal raphe nucleus and they had, for the most part, a lateral localization within the raphe nucleus. Sham-operated rats did not exhibit any upregulation of TPH mRNA. Together, the present results provide the first demonstration that a discreet and selective destruction of serotonergic terminals induces a circumscribed and striking increase in TPH mRNA expression in a subset of brainstem serotonergic neurons projecting to and/or passing through the DLH. On the basis of these results and previous in vivo measurements of TPH activity (e.g., 5-HT synthesis), we suggest that this upregulation in TPH mRNA expression results from the loss of pre-synaptic and/or post-synaptic regulation of serotonin synthesis. These new findings raise important issues related to the repercussions of a local disruption in serotonergic neurotransmission on brain areas remote from the site of injury.

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Section: Introductionsupporting

confidence: 85%

Origin of the serotonergic innervation to the rat dorsolateral hypothalamus: Retrograde transport of cholera toxin and upregulation of tryptophan hydroxylase mRNA expression following selective nerve terminals lesion

Ljubic‐Thibal

Morin

Dikšić

et al. 1999

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“…Possibly, after metabolic clearance of PCPA occurred a resettlement of TPO levels operated by de novo synthesis of that enzyme and subsequent production of serotonin. Hypophagy between 25 th and 30 th day after PCPA microinjection probably reverberate the overexpression of TPO, based on similar conclusions postulated elsewhere (Richard et al 1990, Lima et al 2004. Presumably, the normalization of the serotonin turnover, and possibly high compensatory expression of other anorexigenic pathways (simultaneously to activation of control systems of the energetic balance), would restore the set point of body weight.…”

Section: Discussionsupporting

confidence: 80%

A reassessment of the role of serotonergic system in the control of feeding behavior

Medeiros

Costa-e-Sousa

Olivares

et al. 2005

An. Acad. Bras. Ciênc.

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The role of serotonergic system in the feeding behavior was appraised by electrolytic lesions in the dorsal raphe nucleus (DRN) and administration of para-chlorophenylalanine (PCPA, 3 mg/5 µl, icv). Chronic evaluations were accomplished through 120 and 360 days in PCPA-injected and DRN-lesioned rats, respectively. Acute food intake was evaluated in fasted rats and submitted to injection of PCPA and hydroxytryptophan (LHTP, 30 mg/kg, ip). DRN-lesioned rats exhibited 22-80% increase in food intake up to sixth month, whereas the obesity was evident and sustained by whole period. In PCPA-injected rats was observed an initial increase in the food intake followed by hypophagy from 25 th to 30 th day and a transitory increase of body weight from 5 th to 60 th day. In the acute study, the LHTP reverted partially the PCPA-induced increase in food intake of fasted rats suggesting a sustained capacity of decarboxylation of precursor by serotonergic neurons. Slow restoration of the levels of food intake in DRN-lesioned rats reveals a neuroplasticity in the systems that regulate feeding behavior. A plateau on the body weight curve in lesioned rats possibly represents the establishment of a new and higher set point of energetic balance.

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“…These differences can be explained as resulting from an in vivo interference of pCPA with the synthesis of TPH (Cortes et al, 1993). It has also been shown that pCPA administration provokes a large decrease in the concentration of TRH in the raphe nuclei (Richard et al, 1990). Systemic attempts to deplete 5-HT in the Drosophila CNS by feeding pCPA or AMTP did not result in diminished 5-HT immunoreactivity (Accardo and Neckameyer, unpublished data), although these drugs inhibit 5-HT synthesis when targeted to specific areas of the mammalian brain (Koe and Weismann, 1966;Sourkes et al, 1970;Montine et al, 1992).…”

Section: May 2005mentioning

confidence: 96%

Serotonin synthesis by two distinct enzymes inDrosophila melanogaster

Coleman

Neckameyer

2005

Arch. Insect Biochem. Physiol.

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Annotation of the sequenced Drosophila genome suggested the presence of an additional enzyme with extensive homology to mammalian tryptophan hydroxylase, which we have termed DTRH. In this work, we show that enzymatic analyses of the putative DTRH enzyme expressed in Escherichia coli confirm that it acts as a tryptophan hydroxylase but can also hydroxylate phenylalanine, in vitro. Building upon the knowledge gained from the work in mice and zebrafish, it is possible to hypothesize that DTRH may be primarily neuronal in function and expression, and DTPH, which has been previously shown to have phenylalanine hydroxylation as its primary role, may be the peripheral tryptophan hydroxylase in Drosophila. The experiments presented in this report also show that DTRH is similar to DTPH in that it exhibits differential hydroxylase activity based on substrate. When DTRH uses tryptophan as a substrate, substrate inhibition, catecholamine inhibition, and decreased tryptophan hydroxylase activity in the presence of serotonin synthesis inhibitors are observed. When DTRH uses phenylalanine as a substrate, end product inhibition, increased phenylalanine hydroxylase activity after phosphorylation by cAMP-dependent protein kinase, and a decrease in phenylalanine hydroxylase activity in the presence of the serotonin synthesis inhibitor, alpha-methyl-(DL)-tryptophan are observed. These experiments suggest that the presence of distinct tryptophan hydroxylase enzymes may be evolutionarily conserved and serve as an ancient mechanism to appropriately regulate the production of serotonin in its target tissues.

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Variation of tryptophan-5-hydroxylase concentration in the rat raphe dorsalis nucleus afterp-chlorophenylalanine administration. I. A model to study the turnover of the enzymatic protein

Cited by 32 publications

References 18 publications

Origin of the serotonergic innervation to the rat dorsolateral hypothalamus: Retrograde transport of cholera toxin and upregulation of tryptophan hydroxylase mRNA expression following selective nerve terminals lesion

Origin of the serotonergic innervation to the rat dorsolateral hypothalamus: Retrograde transport of cholera toxin and upregulation of tryptophan hydroxylase mRNA expression following selective nerve terminals lesion

A reassessment of the role of serotonergic system in the control of feeding behavior

Serotonin synthesis by two distinct enzymes inDrosophila melanogaster

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