Characterization of two classes of benzodiazepine binding sites in Schistosoma mansoni

Abstract

SUMMARYAs we have recently shown that GABA should be considered a putative neurotransmitter inSchistosoma mansoni, the present work aimed to search for GABAAreceptors in adult worms using [3H]-flunitrazepam to label the allosteric benzodiazepine binding site which is classically present on GABAAreceptor 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.