title: Amiloride derivatives are effective blockers of insect odorant receptors.
abstract: Heteromeric insect odorant receptors (ORs) form ligand-activated nonselective cation channels in recombinant expression systems. We performed a pharmacological characterization of Drosophila melanogaster and Bombyx mori ORs expressed in the Xenopus laevis oocyte expression system and characterized them using the 2-electrode voltage clamp. We identified amiloride derivatives as high-affinity blockers, which inhibit the ion current through the channel in a low micromolar range. For the heteromeric Drosophila Or47a + DmelOrco receptor, the potency sequence (IC(50)) is HMA [5-(N,N-hexamethylene)amiloride] (3.9 µM), MIA [5-(N-methyl-N-isobutyl)amiloride] (11.0 µM), and DMA [5-(N,N-dimethyl)amiloride] (113.3 µM). Amiloride itself is nearly ineffective. Other tested insect ORs (Drosophila Or49b + DmelOrco, B. mori BmorOr1 + BmorOrco) were blocked in a similar fashion suggesting that the amiloride derivatives were potential general blockers of all receptor combinations. Our results suggest that pyrazine derivatives of amiloride are useful probes to study the mechanism of chemosensory transduction in insects in more detail.
authors: Lehrstuhl für Zellphysiologie, Ruhr-Universität Bochum, Universitätsstrasse 150, 44780 Bochum, Germany.
authors: Katharina
authors: K
authors: Röllecke
authors: Markus
authors: M
authors: Werner
authors: Paul M
authors: PM
authors: Ziemba
authors: Eva M
authors: EM
authors: Neuhaus
authors: Hanns
authors: H
authors: Hatt
authors: Günter
authors: G
authors: Gisselmann
mesh_terms: D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D012831:Bombyx / Q000187:drug effects / Q000378:metabolism; D004331:Drosophila melanogaster / Q000187:drug effects* / Q000378:metabolism; D004566:Electrodes; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D000439:Pentanols / Q000494:pharmacology; D018035:Receptors, Odorant / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis / Q000254:growth & development / Q000378:metabolism
chemical_list: D000439:Pentanols; D018035:Receptors, Odorant; D000584:Amiloride; C005716:amyl acetate