title: Blockade of insect odorant receptor currents by amiloride derivatives.
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.
authors.affiliation: Department of Biological Sciences, Vanderbilt University, Nashville, TN, USA.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Pask
authors.forename: Yuriy V
authors.initials: YV
authors.lastname: Bobkov
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Corey
authors.forename: Barry W
authors.initials: BW
authors.lastname: Ache
authors.forename: Laurence J
authors.initials: LJ
authors.lastname: Zwiebel
mesh_terms: D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000852:Anopheles / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D057809:HEK293 Cells; D006801:Humans; D019476:Insect Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D018408:Patch-Clamp Techniques; D018035:Receptors, Odorant / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D013864:Thioglycolates / Q000494:pharmacology; D014162:Transfection; D014230:Triazoles / Q000494:pharmacology
chemical_list: D019476:Insect Proteins; C572612:N-(4-ethylphenyl)-2-((4-ethyl-5-(3-pyridinyl)-4H-1,2,4-triazol-3-yl)thio)acetamide; D018035:Receptors, Odorant; D013864:Thioglycolates; D014230:Triazoles; D000584:Amiloride