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Comparative pharmacological characterization of D1-like dopamine receptors from Anopheles gambiae, Aedes aegypti and Culex quinquefasciatus suggests pleiotropic signaling in mosquito vector lineages

Overview of attention for article published in Parasites & Vectors, April 2016
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Title
Comparative pharmacological characterization of D1-like dopamine receptors from Anopheles gambiae, Aedes aegypti and Culex quinquefasciatus suggests pleiotropic signaling in mosquito vector lineages
Published in
Parasites & Vectors, April 2016
DOI 10.1186/s13071-016-1477-6
Pubmed ID
Authors

Catherine A. Hill, Trevor Doyle, Andrew B. Nuss, Karin F. K. Ejendal, Jason M. Meyer, Val J. Watts

Abstract

Small molecule antagonists of mosquito dopamine receptors (DARs) are under investigation as a new class of vector-selective insecticides. Antagonists that inhibit the D1-like DARs AaDOP2 and CqDOP2 from the mosquitoes Aedes aegypti L. and Culex quinquefasciatus Say, respectively, also cause larval mortality in bioassays. Here, we report on the orthologous DAR, AgDOP2, from the malaria mosquito Anopheles gambiae Giles that was cloned and pharmacologically characterized in HEK293 cells. Larval bioassays were then conducted to examine the potential of DAR antagonist insecticides against Anopheles vectors. Previous in vitro cAMP accumulation assays demonstrated Gαs coupling for AaDOP2 and CqDOP2 and dose-dependent inhibition by DAR antagonists. We observed a negligible response of AgDOP2 in the cAMP assay, which prompted an investigation of alternative coupling for mosquito DARs. In an in vitro IP-One Gαq second messenger assay of calcium signaling, dopamine stimulation increased IP1 accumulation in AaDOP2-, CqDOP2- and AgDOP2-expressing cells, and DAR antagonists inhibited IP1 signaling in a dose-dependent manner. In larval bioassays, DAR antagonists caused considerable mortality of An. gambiae larvae within 24 h post-exposure. In vitro data reveal pleiotropic coupling of AaDOP2 and CqDOP2 to Gαq and Gαs. In contrast, AgDOP2 appeared to selectively couple to Gαq signaling. In vitro antagonist studies revealed general conservation in pharmacology between mosquito DARs. In vivo data suggest potential for DAR antagonist insecticides against An. gambiae. Sequence conservation among the DOP2 receptors from 15 Anopheles species indicates utility of antagonists to control residual malaria transmission. AgDOP2 Gαq-dependent signaling could be exploited for An. gambiae control via pathway specific antagonists.

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The data shown below were collected from the profiles of 2 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 33 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 33 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 7 21%
Student > Ph. D. Student 5 15%
Student > Master 3 9%
Student > Bachelor 2 6%
Professor 2 6%
Other 7 21%
Unknown 7 21%
Readers by discipline Count As %
Agricultural and Biological Sciences 8 24%
Biochemistry, Genetics and Molecular Biology 2 6%
Medicine and Dentistry 2 6%
Unspecified 2 6%
Veterinary Science and Veterinary Medicine 1 3%
Other 8 24%
Unknown 10 30%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 07 April 2016.
All research outputs
#5,689,916
of 7,516,464 outputs
Outputs from Parasites & Vectors
#1,468
of 2,041 outputs
Outputs of similar age
#190,367
of 270,837 outputs
Outputs of similar age from Parasites & Vectors
#159
of 190 outputs
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