INTRODUCTION: Imaging of the serotonergic innervation of the brain using positron emission tomography (PET) with the serotonin transporter (SERT) ligand [11C] (+)McN5652 might be affected by serotonin in the synaptic cleft if there is relevant interaction between [11C] (+)McN5652 and serotonin at the SERT. The aim of the present study therefore was to pharmacologically characterize the interaction of [11C] (+)McN5652 and serotonin at the SERT. METHODS: In vitro saturation analyses of [3H]serotonin uptake into HEK293 cells stably expressing the human SERT were performed in the absence and presence of unlabelled (+)McN5652. Data were evaluated assuming Michaelis-Menten kinetics. RESULTS: Unlabelled (+)McN5652 significantly reduced the maximal rate of serotonin transport V(max) of SERT without affecting the Michaelis-Menten constant K(M). CONCLUSIONS: This finding indicates that (+)McN5652 inhibits serotonin transport through the SERT in a noncompetitive manner. This might suggest that [11C] (+)McN5652 PET is not significantly affected by endogenous serotonin.
INTRODUCTION: Imaging of the serotonergic innervation of the brain using positron emission tomography (PET) with the serotonin transporter (SERT) ligand [11C] (+)McN5652 might be affected by serotonin in the synaptic cleft if there is relevant interaction between [11C] (+)McN5652 and serotonin at the SERT. The aim of the present study therefore was to pharmacologically characterize the interaction of [11C] (+)McN5652 and serotonin at the SERT. METHODS: In vitro saturation analyses of [3H]serotonin uptake into HEK293 cells stably expressing the humanSERT were performed in the absence and presence of unlabelled (+)McN5652. Data were evaluated assuming Michaelis-Menten kinetics. RESULTS: Unlabelled (+)McN5652 significantly reduced the maximal rate of serotonin transport V(max) of SERT without affecting the Michaelis-Menten constant K(M). CONCLUSIONS: This finding indicates that (+)McN5652 inhibits serotonin transport through the SERT in a noncompetitive manner. This might suggest that [11C] (+)McN5652 PET is not significantly affected by endogenous serotonin.
Authors: M Reimold; M N Smolka; G Schumann; A Zimmer; J Wrase; K Mann; X-Z Hu; D Goldman; G Reischl; C Solbach; H-J Machulla; R Bares; A Heinz Journal: J Neural Transm (Vienna) Date: 2007-01-18 Impact factor: 3.575
Authors: Jeffrey M Miller; Erin L Kinnally; R Todd Ogden; Maria A Oquendo; J John Mann; Ramin V Parsey Journal: Synapse Date: 2009-07 Impact factor: 2.562
Authors: Ursula F Bailer; Guido K Frank; Julie C Price; Carolyn C Meltzer; Carl Becker; Chester A Mathis; Angela Wagner; Nicole C Barbarich-Marsteller; Cinnamon S Bloss; Karen Putnam; Nicholas J Schork; Anthony Gamst; Walter H Kaye Journal: Psychiatry Res Date: 2012-11-13 Impact factor: 3.222