The Acute Effects of Reserpine and NSD-1015 on the Brain Serotonin Synthesis Rate Measured by an Autoradiographic Method

Mück‐Šeler, Dorotea; Dikšić, Mirko

doi:10.1016/0893-133x(94)00084-d

Cited by 32 publications

(15 citation statements)

References 31 publications

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“…Blockade of terminal 5-HT 1B autoreceptors with GR 127935 increased 5-HIAA concentrations and the 5-HIAA/5-HT ratio considerably more than 5-HTP accumulation in non-pretreated animals (Stenfors et al 1999, the present study). However, it is also possible that the difference is due to an effect introduced by NSD 1015, since this compound may itself increase 5-HT synthesis (Mück-Šeler and Diksic 1995). If so, NSD 1015 is not the optimal decarboxylase inhibitor for studies of the 5-HTP accumulation in vivo.…”

Section: Discussionmentioning

confidence: 97%

Failure to detect in vivo inverse agonism of the 5-HT 1B receptor antagonist SB-224289 in 5-HT-depleted guinea-pigs

Stenfors

Ross

2002

Naunyn-Schmiedeberg's Archives of Pharmacology

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The possibility that 5-HT(1B) receptors display constitutive activity in vivo, i.e. have a basal agonist-independent activity, was examined in guinea-pigs depleted of endogenous brain 5-HT by pre-treatment with reserpine. Under these conditions (5 mg/kg s.c. reserpine 24 h before the experiment), hypothalamic 5-HT concentration was reduced by more than 97%. In reserpine-treated animals, 5-HT synthesis [measured as the accumulation of 5-hydroxytryptophan (5-HTP) after inhibition of the aromatic amino acid decarboxylase with m-hydroxybenzylhydrazine dihydrochloride (NSD 1015, 100 mg/kg s.c.)] was similar to that in non-treated guinea-pigs. The formation of 5-hydroxyindoleacetic acid (5-HIAA) was enhanced by reserpine treatment. The 5-HT(1B/1D) receptor agonist 3-( N-methylpyrrolidin-2- R-ylmethyl)-5-(3-nitropyrid-2-ylamino)-1 H-indole (CP-135,807) decreased 5-HT synthesis and 5-HIAA formation to the same extent in reserpine-treated and naive animals showing that the terminal 5-HT(1B) autoreceptors were functionally active during reserpine treatment. The 5-HT(1B) inverse agonist 1'-methyl-5-([2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl)-4-yl]carbonyl)-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine] hydrochloride (SB-224289, 4 mg/kg s.c.), which in naive guinea-pigs significantly enhanced 5-HIAA formation and tended to enhance 5-HT synthesis, had no effect in the reserpine-treated animals. Likewise, SB-224289 did not change the rectal temperature in reserpine-treated guinea-pigs although the agonist CP-135,807 had a significant hypothermic effect in these animals. It is concluded that no constitutive activity of 5-HT(1B) autoreceptors (5-HIAA formation) or 5-HT(1B) heteroreceptors (rectal temperature) could be detected under the in vivo experimental conditions used.

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Section: Discussionmentioning

confidence: 97%

Failure to detect in vivo inverse agonism of the 5-HT 1B receptor antagonist SB-224289 in 5-HT-depleted guinea-pigs

Stenfors

Ross

2002

Naunyn-Schmiedeberg's Archives of Pharmacology

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“…The hypothesis related to a need to replenish the neuronal releasable pool is also supported by a reported increase in the extracellular fluorescence and without a change in the intracellular fluorescence for 5-HT after fluoxetine treatment [9], the results of which can be observed only if 5-HT synthesis has been increased to replenish the depleted extracellular pool. Similarly, other drugs that release and/or reduce intracellular 5-HT stores such as reserpine, 3,4-methylenedioxymethamphetamine and fenfluramine, produce increases in 5-HT synthesis at the terminal areas [16,24,29,56]. Further, fluoxetine increased 5-HT synthesis at several brain areas in conscious rats [25,48].…”

Section: Discussionmentioning

confidence: 99%

Acute citalopram has different effects on regional 5-HT synthesis in FSL, FRL, and SDP rats: An autoradiographic evaluation

Kanemaru

Hasegawa

Nishi

et al. 2008

Brain Research Bulletin

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In this study, we measured the effect of an acute treatment of citalopram on 5-HT synthesis in a genetic rat model of depression, the Flinders Sensitive Line (FSL) rats, their counterparts, the Flinders Resistant Line (FRL) rats, and outbred Sprague-Dawley (SPD) rats, using the α-[ 14 C]methyl-Ltryptophan (α-MTrp) autoradiographic method. A comparison of 5-HT synthesis in the FSL rats treated with citalopram (FSL-CTP) and those treated with saline (FSL-SAL) indicate that citalopram reduces global 5-HT synthesis in the FSL rats, as well as in all the brain areas investigated. The reduced synthesis was also observed in the dorsal raphe nucleus (DR) and the median raphe nucleus (MR). The comparison of the synthesis between the citalopram treated SPD rats (SPD-CTP) and the saline treated SPD rats (SPD-SAL) revealed a global increase of 5-HT synthesis in the SPD-CTP group, as well as an increase in some terminal areas, but a reduction in the DR and the MR. In contrast to the reduction throughout the brain in the FSL rats, the FRL rats treated with citalopram (FRL-CTP), when compared to the saline group (FRL-SAL), showed a global increase of 5-HT synthesis, as well as in most of the terminal areas and in the DR and the MR. The reduction of 5-HT synthesis throughout the brain in the FSL rats is likely a result of reported supersensitivity of the 5-HT 1A receptors. Comparing changes in the SPD, FRL, and FSL rats treated with citalopram to their respective controls (saline treated rats), the FSL rats treated acutely with citalopram were the only rats that exhibited lower 5-HT synthesis rates in all of the limbic areas, the basal ganglia, and the neocortices. This may be related to the pathophysiological basis of depressive characteristics in FSL rats. The citalopram treatment produced unexpected results in the FRL rats: 5-HT synthesis was elevated not only in most of the terminal areas, but also in the cell body areas, the DR and MR. The increase of 5-HT synthesis throughout the brain in the FRL rats is likely a result of the reported subsensitivity of the 5-HT 1A receptors, and possibly other sites through which 5-HT synthesis could be controlled (e.g., 5-HT 1B ). In addition differences in intracellular signaling could be at least in part responsible for these differences. 4Correspondence to;

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“…Then 100 μL of the incubation cocktail was added and the mixture was incubated at 30°C for an additional 10min to initiate the reaction. The incubation mixture was prepared by adding 0.25mM L – tryptophan, 0.4 mM (6R)-l-erythro-tetrahydrobiopterin, 0.5 mM NADH (nicotinamide adenine dinucleotide, 1 mM NSD-1015 (aromatic amino acid decarboxylase inhibitor/3-Hydroxybenzylhydrazine dihydrochloride; Sigma), 4.5 μg/mL dihydropteridine reductase from sheep liver (Sigma), 2 mg/mL catalase (Sigma), and 0.1M potassium phosphate (pH 6.9) (Sigma) [47]. NSD 1015 is added to aid in the accumulation of 5-hydroxy tryptophan the direct product of TPH’s enzymatic activity.…”

Section: Methodsmentioning

confidence: 99%

Functional constituents of a local serotonergic system, intrinsic to the human coronary artery smooth muscle cells

et al. 2015

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Human coronary artery smooth muscle cells (HCASMCs) play an important role in the pathogenesis of coronary atherosclerosis and coronary artery diseases (CAD). Serotonin is a mediator known to produce vascular smooth muscle cell (VSMC) mitogenesis and contribute to coronary atherosclerosis. We hypothesize that the human coronary artery smooth muscle cell possesses certain functional constituents of the serotonergic system such as: tryptophan hydroxylase and serotonin transporter. Our aim was to examine the presence of functional tryptophan hydroxylase-1 (TPH1) and serotonin transporter (SERT) in HCASMCs. The mRNA transcripts by qPCR and protein expression by Western blot of TPH1 and SERT were examined. The specificity and accuracy of the primers were verified using DNA gel electrophoresis and sequencing of qPCR products. The functionality of SERT was examined using a fluorescence dye-based serotonin transporter assay. The enzymatic activity of TPH was evaluated using UPLC. The HCASMCs expressed both mRNA transcripts and protein of SERT and TPH. The qPCR showed a single melt curve peak for both transcripts and in sequence analysis the amplicons were aligned with the respective genes. SERT and TPH enzymatic activity was present in the HCASMCs. Taken together, both TPH and SERT are functionally expressed in HCASMCs. These findings are novel and represent an initial step in examining the clinical relevance of the serotonergic system in HCASMCs and its role in the pathogenesis of coronary atherosclerosis and CAD.

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The Acute Effects of Reserpine and NSD-1015 on the Brain Serotonin Synthesis Rate Measured by an Autoradiographic Method

Cited by 32 publications

References 31 publications

Failure to detect in vivo inverse agonism of the 5-HT 1B receptor antagonist SB-224289 in 5-HT-depleted guinea-pigs

Failure to detect in vivo inverse agonism of the 5-HT 1B receptor antagonist SB-224289 in 5-HT-depleted guinea-pigs

Acute citalopram has different effects on regional 5-HT synthesis in FSL, FRL, and SDP rats: An autoradiographic evaluation

Functional constituents of a local serotonergic system, intrinsic to the human coronary artery smooth muscle cells

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