Actions of Avermectin B(1a) on the Gamma-Aminobutyric Acid(A) Receptor and Chloride Channels in Rat Brain

摘要

The interaction of avermectin B1a (AVM) with the gamma-aminobutyric acid (GABA) receptor of rat brain was studied using radioactive ligand binding and tracer ion flux assays. Avermectin potentiated the binding of Hydrogen 3 flunitrazepam and inhibited the binding of both Hydrogen 3 muscimol and Sulfur 35 t-butylbicyclophosphorothionate to the GABA sub A receptor. Inhibition of muscimol binding by AVM suggested competitive displacement. Two kinds of Chloride 36 (CL) flux were studied. The Chlorine 36 efflux from preloaded microsacs was potentiated by AVM and was highly inhibited by the CL-channel blocker4,4'-diisothiocyano2,2'-stilbenedisulfonic acid (DIDS). However, it was not potentiated by GABA nor was it sensitive to the convulsants picrotoxin or bicuculline. On the other hand, Chlorine 36-influx measurement in a different microsac preparation of rat brain was very sensitive to GABA sub A and other by GABA-dependent Manner, but to only 35% of the Cl influx induced by GABA. The AVM-induced Chlorine 36 influx was totally blocked by bicuculline. It is suggested that AVM opens the GABA sub A-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.