Blockade of Insect Odorant Receptor Currents by Amiloride Derivatives

Overview

Journal Chem Senses

Publisher Oxford University Press

Specialty Biochemistry

Date 2013 Jan 8

PMID 23292750

Citations 22

Authors

Gregory M Pask

Yuriy V Bobkov

Elizabeth A Corey

Barry W Ache

Laurence J Zwiebel

Affiliations

Soon will be listed here.

Abstract

Insect odorant receptors (ORs) function as heteromeric odorant-gated ion channels consisting of a conserved coreceptor, Orco, and an odorant-sensitive tuning subunit. Although some OR modulators have been identified, an extended library of pharmacological tools is currently lacking and would aid in furthering our understanding of insect OR complexes. We now demonstrate that amiloride and several derivatives, which have been extensively used as blockers for various ion channels and transporters, also block odorant-gated currents from 2 OR complexes from the malaria vector mosquito Anopheles gambiae. In addition, both heteromeric and homomeric ORs were susceptible to amiloride blockade when activated by VUAA1, an agonist that targets the Orco channel subunit. Amiloride derivatives therefore represent a valuable class of channel blockers that can be used to investigate the pharmacological and biophysical properties of insect OR function.

Citing Articles

Functional expression and ligand identification of homo- and heteromeric Drosophila melanogaster CO2 receptors in the Xenopus laevis oocyte system.

Ziemba P, Mueck A, Gisselmann G, Stoertkuhl K PLoS One. 2023; 18(12):e0295404.

PMID: 38157355 PMC: 10756536. DOI: 10.1371/journal.pone.0295404.

Elucidation of the structural basis for ligand binding and translocation in conserved insect odorant receptor co-receptors.

Pacalon J, Audic G, Magnat J, Philip M, Golebiowski J, Moreau C Nat Commun. 2023; 14(1):8182.

PMID: 38081900 PMC: 10713630. DOI: 10.1038/s41467-023-44058-5.

Odorant inhibition in mosquito olfaction mediated by inverse agonists.

Xu P, Choo Y, Leal W Biochem Biophys Res Commun. 2022; 609:156-162.

PMID: 35430419 PMC: 10540603. DOI: 10.1016/j.bbrc.2022.04.015.

Mosquito odorant receptor sensitive to natural spatial repellents and inhibitory compounds.

Xu P, Choo Y, An S, Leal G, Leal W Insect Biochem Mol Biol. 2022; 144:103763.

PMID: 35364281 PMC: 10540633. DOI: 10.1016/j.ibmb.2022.103763.

Altered functional properties of the codling moth Orco mutagenized in the intracellular loop-3.

Bobkov Y, Walker Iii W, Cattaneo A Sci Rep. 2021; 11(1):3893.

PMID: 33594162 PMC: 7887336. DOI: 10.1038/s41598-021-83024-3.

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