Medical College of Wisconsin
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Kinetic profiling an abundantly expressed planarian serotonergic GPCR identifies bromocriptine as a perdurant antagonist. Int J Parasitol Drugs Drug Resist 2016 12;6(3):356-363

Date

07/12/2016

Pubmed ID

27397764

Pubmed Central ID

PMC5196488

DOI

10.1016/j.ijpddr.2016.06.002

Scopus ID

2-s2.0-85003481158   12 Citations

Abstract

The diversity and uniqueness of flatworm G protein coupled receptors (GPCRs) provides impetus for identifying ligands useful as tools for studying flatworm biology, or as therapeutics for treating diseases caused by parasitic flatworm infections. To catalyse this discovery process, technologies optimized for mammalian GPCR high throughput screening need be transposed for screening flatworm GPCRs. Here, we demonstrate the utility of a genetically encoded cAMP biosensor for resolving the properties of an abundantly expressed planarian serotonergic GPCR (S7.1R). Application of this methodology resolved the real time kinetics of GPCR modulation by ligands and demonstrated a marked difference in the kinetic action of antagonists at S7.1R. Notably, bromocriptine caused a protracted inhibition of S7.1R activity in vitro and a protracted paralysis of planarian movement, replicating the effect of S7.1R in vivo RNAi. The lengthy inhibition of function caused by bromocriptine at this abundantly expressed GPCR provides a useful tool to ablate serotonergic signaling in vivo, and is a noteworthy feature for exploitation as an anthelmintic vulnerability.

Author List

Chan JD, Grab T, 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
Bromocriptine
Drug Evaluation, Preclinical
Kinetics
Locomotion
Planarians
Receptors, G-Protein-Coupled
Serotonergic Neurons
Serotonin Antagonists
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