Characterization of two classes of benzodiazepine binding sites in S chistosoma mansoni

As we have recently shown that GABA should be considered a putative neurotransmitter in Schistosoma mansoni , the present work aimed to search for GABA A receptors in adult worms using [ 3 H]-flunitrazepam to label the allosteric benzodiazepine binding site which is classically present on GABA A receptor complexes. We detected a large population ( B max =8·25±1·1 pmol . mg protein −1 ) of high affinity ( K d =33·6±1·5 n m ) 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 (IC 50 =85 n m ) by [ 3 H]-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.