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The anthelmintic praziquantel is a human serotoninergic G-protein-coupled receptor ligand.
- Source :
-
Nature communications [Nat Commun] 2017 Dec 05; Vol. 8 (1), pp. 1910. Date of Electronic Publication: 2017 Dec 05. - Publication Year :
- 2017
-
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 5HT <subscript>2B</subscript> 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.
- Subjects :
- Animals
Anthelmintics pharmacology
Cell Line
Computer Simulation
Drug Partial Agonism
Female
Humans
Mice
Myography
Praziquantel pharmacology
Receptor, Serotonin, 5-HT2B drug effects
Receptor, Serotonin, 5-HT2B metabolism
Schistosomiasis mansoni drug therapy
Serotonin 5-HT2 Receptor Agonists pharmacology
Anthelmintics metabolism
Mesenteric Arteries drug effects
Mesenteric Veins drug effects
Praziquantel metabolism
Schistosoma mansoni drug effects
Serotonin 5-HT2 Receptor Agonists pharmacokinetics
Vasoconstriction drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 8
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 29208933
- Full Text :
- https://doi.org/10.1038/s41467-017-02084-0