External amino acid residues of insect GABA receptor channels dictate the action of the isoxazoline ectoparasiticide fluralaner.

Background: Fluralaner is the first isoxazoline ectoparasiticide developed to protect companion animals from fleas and ticks. Fluralaner primarily inhibits arthropod γ-aminobutyric acid receptors (GABARs), which are ligand-gated ion channels comprising five subunits arranged around the channel pore. We previously reported that the action site of fluralaner resides at the M1-M3 transmembrane interface between adjacent GABAR subunits.

Effects of intersubunit amino acid substitutions on GABA receptor sensitivity to the ectoparasiticide fluralaner.

The isoxazoline ectoparasiticide fluralaner exerts antiparasitic effects by inhibiting the function of γ-aminobutyric acid (GABA) receptors (GABARs). The present study was conducted to identify the amino acid residues that contribute to the high sensitivity of insect GABARs to fluralaner. We generated housefly (Musca domestica) GABARs with amino acid substitutions in the first through third α-helical transmembrane segments (TM1-TM3) of the RDL subunit using site-directed mutagenesis and examined the effects of the substitutions on the sensitivity of GABARs expressed in Xenopus oocytes to fluralaner using two-electrode voltage clamp electrophysiology.

A Single Amino Acid Substitution in the Third Transmembrane Region Has Opposite Impacts on the Selectivity of the Parasiticides Fluralaner and Ivermectin for Ligand-Gated Chloride Channels.

Fluralaner (Bravecto) is a recently marketed isoxazoline ectoparasiticide. This compound potently inhibits GABA-gated chloride channels (GABACls) and less potently glutamate-gated chloride channels (GluCls) in insects. The mechanism underlying this selectivity is unknown.

Photocatalysis using a Wide Range of the Visible Light Spectrum: Hydrogen Evolution from Doped AgGaS2.

Doping of nickel into AgGaS2 yields a new absorption band, at a wavelength longer than the intrinsic absorption band of the AgGaS2 host. The doped nickel forms an electron donor level in a forbidden band of AgGaS2 . The nickel-doped AgGaS2 with rhodium co-catalyst shows photocatalytic activity for sacrificial H2 evolution under the light of up to 760 nm due to the transition from the electron donor level consisting of Ni(2+) to the conduction band of AgGaS2 .