Actions of avermectin B1a on the γ‐aminobutyric AcidA receptor and chloride channels in rat brain

Publisher Website
Google Scholar
Abstract
The interaction of avermectin B1a (AVM) with the γ‐aminobutyric acid (GABA) receptor of rat brain was studied using radioactive ligand binding and tracer ion flux assays. Avermectin potentiated the binding of [3H]flunitrazepam and inhibited the binding of both [3H]muscimol and [35S]t‐butylbicyclo‐phosphorothionate to the GABAA receptor. Inhibition of muscimol binding by AVM suggested competitive displacement. Two kinds of 36chloride (Cl) flux were studied. The 36Cl efflux from preloaded microsacs was potentiated by AVM and was highly inhibited by the Cl‐channel blocker 4,4′‐diisothiocyano‐2,2′‐stilbenedisulfonic acid (DIDS). However, it was not potentiated by GABA nor was it sensitive to the convulsants picrotoxin or bicuculline. On the other hand, 36Cl‐influx measurement in a different microsac preparation of rat brain was very sensitive to GABA and other GABA‐ergic drugs. Avermectin induced 36Cl influx into these microsacs in a dose–dependent manner, but to only 35% of the maximal influx induced by GABA. The AVM‐induced 36Cl influx was totally blocked by bicuculline. It is suggested that AVM opens the GABAA‐receptor Cl channel by binding to the GABA recognition site and acting as a partial receptor agonist, and also opens a voltage–dependent Cl channel which is totally insensitive to GABA but is very sensitive to DIDS.