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The anthelmintic praziquantel is a human serotoninergic G-protein-coupled receptor ligand. Nat Commun 2017 Dec 05;8(1):1910

Date

12/07/2017

Pubmed ID

29208933

Pubmed Central ID

PMC5716991

DOI

10.1038/s41467-017-02084-0

Scopus ID

2-s2.0-85037138864 (requires institutional sign-in at Scopus site)   60 Citations

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.

Author List

Chan JD, Cupit PM, Gunaratne GS, McCorvy JD, Yang Y, Stoltz K, Webb TR, Dosa PI, Roth BL, Abagyan R, Cunningham C, Marchant JS

Authors

Jonathan S. Marchant PhD Chair, Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
John McCorvy PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Anthelmintics
Cell Line
Computer Simulation
Drug Partial Agonism
Female
Humans
Mesenteric Arteries
Mesenteric Veins
Mice
Myography
Praziquantel
Receptor, Serotonin, 5-HT2B
Schistosoma mansoni
Schistosomiasis mansoni
Serotonin 5-HT2 Receptor Agonists
Vasoconstriction