title: An inhibitor of Na(+)/Ca(2+) exchange blocks activation of insect olfactory receptors.
abstract: Earlier we showed that the Na(+)/Ca(2+) exchanger inhibitor, KB-R7943, potently blocks the odor-evoked activity of lobster olfactory receptor neurons. Here we extend that finding to recombinant mosquito olfactory receptors stably expressed in HEK cells. Using whole-cell and outside-out patch clamping and calcium imaging, we demonstrate that KB-R7943 blocks both the odorant-gated current and the odorant-evoked calcium signal from two different OR complexes from the malaria vector mosquito, Anopheles gambiae, AgOr48+AgOrco and AgOr65+AgOrco. Both heteromeric and homomeric (Orco alone) OR complexes were susceptible to KB-R7943 blockade when activated by VUAA1, an agonist that targets the Orco channel subunit, suggesting the Orco subunit may be the target of the drug's action. KB-R7943 represents a valuable tool to further investigate the functional properties of arthropod olfactory receptors and raises the interesting specter that activation of these ionotropic receptors is directly or indirectly linked to a Na(+)/Ca(2+) exchanger, thereby providing a template for drug design potentially allowing improved control of insect pests and disease vectors.
authors.affiliation: Whitney Laboratory, Center for Smell and Taste, McKnight Brain Institute, United States. Electronic address: bobkov@whitney.ufl.edu.
authors.forename: Y
authors.initials: Y
authors.lastname: Bobkov
authors.affiliation: Whitney Laboratory, Center for Smell and Taste, McKnight Brain Institute, United States.
authors.forename: E
authors.initials: E
authors.lastname: Corey
authors.affiliation: Whitney Laboratory, Center for Smell and Taste, McKnight Brain Institute, United States; Depts. of Biology and Neuroscience, Univ. of Florida, Gainesville, FL 32610, United States.
authors.forename: B
authors.initials: B
authors.lastname: Ache
mesh_terms: D000818:Animals; D000852:Anopheles / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D019476:Insect Proteins / Q000819:agonists / Q000037:antagonists & inhibitors*; D015640:Ion Channel Gating; D055503:Protein Multimerization; D018035:Receptors, Odorant / Q000819:agonists / Q000037:antagonists & inhibitors*; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors*; D013864:Thioglycolates / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology
chemical_list: C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; 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; D019831:Sodium-Calcium Exchanger; D013864:Thioglycolates; D014230:Triazoles; D013890:Thiourea
keywords: Inhibition; Ionotropic receptor; Mosquito olfactory receptor; Sodium calcium exchanger