Glutamate-mediated signaling in Schistosoma mansoni: a novel glutamate receptor is expressed in neurons and the female reproductive tract.

l-Glutamate is a major neurotransmitter of both vertebrates and invertebrates. Earlier studies have shown that glutamate stimulates neuromuscular activity in the bloodfluke, Schistosoma mansoni, but its mode of action is unknown. Here we describe a novel glutamate receptor in S. mansoni (SmGluR), the first of its kind to be identified in a parasitic flatworm. SmGluR belongs to the G protein-coupled receptor (GPCR) superfamily and is distantly related to metabotropic glutamate receptors from other species. The full-length receptor cDNA was cloned, stably expressed in HEK-293 cells and shown to be activated by glutamate, whereas aspartate and the glutamate derivative, gamma-aminobutyric acid (GABA) had no significant effect. Among the classical (mammalian) agonists and antagonists tested, only LY341495 was able to interact with the schistosome receptor, suggesting that the pharmacological profile of SmGluR is substantially different from that of receptors in the host. The presence of SmGluR in the parasite was verified by immunoprecipitation and Western blot analyses, using a specific peptide antibody. Confocal immunolocalization studies revealed that SmGluR is strongly expressed in the nervous system of adult worms and larvae. In the adults, the receptor was detected in the longitudinal nerve cords and cerebral commissures, as well as the peripheral nerve fibers and plexuses innervating the acetabulum and the somatic musculature. Outside the nervous system, SmGluR was detected along the length of the female reproductive system, including the oviduct, ootype and the uterus. A comparative expression analysis at the RNA level revealed that SmGluR is expressed at about the same level in cercaria and adult stages, as determined by quantitative reverse-transcription PCR. The results identify SmGluR as an important neuronal receptor and provide the first molecular evidence for a glutamate signaling system in schistosomes. Copyright Â