Amiloride Derivatives Are Effective Blockers of Insect Odorant Receptors

作者：Roellecke Katharina; Werner Markus; Ziemba Paul M; Neuhaus Eva M; Hatt Hanns; Gisselmann Guenter^*

来源：Chemical Senses, 2013, 38(3): 231-236.

DOI：10.1093/chemse/bjs140

• Bombyx mori
• chemosensation
• Drosophila melanogaster
• olfaction
• voltage clamp
• Xenopus laevis oocytes

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 (IC50) is HMA [5-(N,N-hexamethylene)amiloride] (3.9 M), MIA [5-(N-methyl-N-isobutyl)amiloride] (11.0 M), and DMA [5-(N,N-dimethyl)amiloride] (113.3 M). 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.

• 出版日期2013-3