Medical College of Wisconsin
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Ca²⁺ channels and praziquantel: a view from the free world. Parasitol Int 2013 Dec;62(6):619-28

Date

12/19/2012

Pubmed ID

23246536

Pubmed Central ID

PMC3610807

DOI

10.1016/j.parint.2012.12.001

Scopus ID

2-s2.0-84885379777   31 Citations

Abstract

Targeting the cellular Ca(2+) channels and pumps that underpin parasite Ca(2+) homeostasis may realize novel antihelmintic agents. Indeed, the antischistosomal drug praziquantel (PZQ) is a key clinical agent that has been proposed to work in this manner. Heterologous expression data has implicated an action of PZQ on voltage-operated Ca(2+) channels, although the relevant in vivo target of this drug has remained undefined over three decades of clinical use. The purpose of this review is to bring new perspective to this issue by discussing the potential utility of free-living planarian flatworms for providing new insight into the mechanism of PZQ action. First, we discuss in vivo functional genetic data from the planarian system that broadly supports the molecular data collected in heterologous systems and the 'Ca(2+) hypothesis' of PZQ action. On the basis of these similarities we highlight our current knowledge of platyhelminth voltage operated Ca(2+) channels, their unique molecular pharmacology and the downstream functional PZQ interactome engaged by dysregulation of Ca(2+) influx that has potential to yield novel antischistosomal targets. Overall the broad dataset underscores a common theme of PZQ-evoked disruptions of Ca(2+) homeostasis in trematodes, cestodes and turbellarians, and showcases the utility of the planarian model for deriving insight into drug action and targets in parasitic flatworms.

Author List

Chan JD, Zarowiecki M, Marchant JS

Author

Jonathan S. Marchant PhD Chair, 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
Calcium Channels
Calcium Signaling
Helminthiasis
Homeostasis
Planarians
Platyhelminths
Praziquantel
Schistosoma
Schistosomiasis
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