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Characterization of two classes of benzodiazepine binding sites in Schistosoma mansoni

Published online by Cambridge University Press:  22 February 2007

F. NOËL ,
D. L. MENDONÇA-SILVA ,
J-P. B. THIBAUT  and
D. V. S. LOPES
F. NOËL*
Affiliation:
Departamento de Farmacologia Básica e Clínica, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Cidade Universitária, 21941-590, Rio de Janeiro, Brasil
D. L. MENDONÇA-SILVA
Affiliation:
Departamento de Farmacologia Básica e Clínica, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Cidade Universitária, 21941-590, Rio de Janeiro, Brasil
J-P. B. THIBAUT
Affiliation:
Departamento de Farmacologia Básica e Clínica, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Cidade Universitária, 21941-590, Rio de Janeiro, Brasil
D. V. S. LOPES
Affiliation:
Departamento de Farmacologia Básica e Clínica, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Cidade Universitária, 21941-590, Rio de Janeiro, Brasil
*
*Corresponding author. Tel: +55 (21) 2562 6732. E-mail: [email protected]
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Summary

As we have recently shown that GABA should be considered a putative neurotransmitter in Schistosoma mansoni, the present work aimed to search for GABAA receptors in adult worms using [3H]-flunitrazepam to label the allosteric benzodiazepine binding site which is classically present on GABAA receptor complexes. We detected a large population (Bmax=8·25±1·1 pmol . mg protein−1) of high affinity (Kd=33·6±1·5 nm) binding sites for flunitrazepam. These sites harboured a singular pharmacological modulation that does not fit well with a mammalian central benzodiazepine receptor, mainly due to a very high affinity for Ro5-4864 and a very low affinity for clonazepam. We also detected a second population of benzodiazepine binding sites labelled with high affinity (IC50=85 nm) by [3H]-PK11195, a selective ligand of the mammalian peripheral benzodiazepine receptor. In conclusion, this work describes the pharmacological properties of a large population of central-like benzodiazepine receptors supporting their study as putative new targets for the development of anti-parasitic agents. We also describe, for the first time, the presence of peripheral benzodiazepine receptors in this parasite.

Keywords

Schistosoma mansonibenzodiazepineflunitrazepamPK11195GABAplatyhelminth
Type
Research Article
Information
Parasitology , Volume 134 , Issue 7 , July 2007 , pp. 1003 - 1012
Copyright
Copyright © Cambridge University Press 2007

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