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The anthelmintic praziquantel is a human serotoninergic G-protein-coupled receptor ligand.

ABSTRACT: Schistosomiasis is a debilitating tropical disease caused by infection with parasitic blood flukes. Approximately 260 million people are infected worldwide, underscoring the clinical and socioeconomic impact of this chronic infection. Schistosomiasis is treated with the drug praziquantel (PZQ), which has proved the therapeutic mainstay for over three decades of clinical use. However, the molecular target(s) of PZQ remain undefined. Here we identify a molecular target for the antischistosomal eutomer?-?(R)-PZQ?-?which functions as a partial agonist of the human serotoninergic 5HT2B receptor. (R)-PZQ modulation of serotoninergic signaling occurs over a concentration range sufficient to regulate vascular tone of the mesenteric blood vessels where the adult parasites reside within their host. These data establish (R)-PZQ as a G-protein-coupled receptor ligand and suggest that the efficacy of this clinically important anthelmintic is supported by a broad, cross species polypharmacology with PZQ modulating signaling events in both host and parasite.

SUBMITTER: Chan JD

PROVIDER: S-EPMC5716991 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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The anthelmintic praziquantel is a human serotoninergic G-protein-coupled receptor ligand.

Chan John D JD Cupit Pauline M PM Gunaratne Gihan S GS McCorvy John D JD Yang Yang Y Stoltz Kristen K Webb Thomas R TR Dosa Peter I PI Roth Bryan L BL Abagyan Ruben R Cunningham Charles C Marchant Jonathan S JS

Nature communications 20171205 1

Schistosomiasis is a debilitating tropical disease caused by infection with parasitic blood flukes. Approximately 260 million people are infected worldwide, underscoring the clinical and socioeconomic impact of this chronic infection. Schistosomiasis is treated with the drug praziquantel (PZQ), which has proved the therapeutic mainstay for over three decades of clinical use. However, the molecular target(s) of PZQ remain undefined. Here we identify a molecular target for the antischistosomal eut ...[more]

PMID: 29208933

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The anthelmintic praziquantel is a human serotoninergic G-protein-coupled receptor ligand.

Publications

The anthelmintic praziquantel is a human serotoninergic G-protein-coupled receptor ligand.

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