Pessoa_2005_Biochem.Pharmacol_69_1509

Several studies have suggested that l-glutamate is a putative neurotransmitter in Schistosoma mansoni. Recently, we detected the presence of low-affinity binding sites for [(3)H]kainic acid in the heterogeneous (P(1)) subcellular fraction of S. mansoni. In an attempt to characterize N-methyl-d-aspartate (NMDA) receptors in this worm, we performed binding assays with [(3)H]MK-801, a NMDA non-competitive antagonist, in the P(1) fraction of adult S. mansoni. In competition experiments, MK-801 (IC(50) approximately 200 microM) and ketamine (IC(50) approximately 500 microM) exhibited a low affinity for the sites labeled with [(3)H]MK-801. Along with the lack of modulation of this binding by glutamatergic agonists and antagonists and the absence of stereoselectivity for MK-801 isomers, these results suggest that [(3)H]MK-801 could label a site different from the classical NMDA receptor in S. mansoni. Based on the evidences that MK-801 interacts with mammalian muscle and central nervous system nicotinic receptors as a low-affinity noncompetitive antagonist, we have investigated the effects of MK-801 on the nicotine-induced flaccid paralysis of the worm, in vivo. The motility of S. mansoni was quantified by image analysis through a measure of displacement of the worm's extremities. In the presence of (-)-nicotine (10-100 microM), we observed an immediate paralysis of the worms, that was inhibited by 1mM MK-801. Besides nicotine, choline (10-50mM) was also able to inhibit the worm's motility. As a conclusion, we suggest that [(3)H]MK-801 binds to nicotinic receptors, and not NMDA receptors, in subcellular fractions of S. mansoni.