Stimulation of benzodiazepine binding to rat brain membranes and solubilized receptor complex by avermectin B1a and gamma-aminobutyric acid.
The binding of [3H]flunitrazepam to benzodiazepine receptors in synaptic membranes and a digitonin-solubilized receptor fraction of rat brain is increased by avermectin B1a and gamma-aminobutyric acid (GABA). The effects of avermectin B1a and GABA are both sensitive to inhibition by (+)-bicuculline. Avermectin B1a and GABA both decrease the Kd and increase the Bmax of [3H]flunitrazepam binding to membranes. Kinetic analysis of the binding of [3H]flunitrazepam to rat brain membranes indicates that avermectin B1a and GABA reduce the rate constants of both association and dissociation between the ligand and the receptor. These results suggest a similar mechanism of modulation of benzodiazepine binding by avermectin B1a and GABA. This modulation may involve in interaction among the receptors for benzodiazepine, GABA and avermectin B1a.
D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D014151:Anti-Anxiety Agents / Q000378:metabolism*; D001640:Bicuculline / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D005445:Flunitrazepam / Q000378:metabolism*; D007473:Ion Channels / Q000378:metabolism; D007559:Ivermectin / Q000031:analogs & derivatives*; D007783:Lactones / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011955:Receptors, Drug / Q000378:metabolism*; D011963:Receptors, GABA-A; D013570:Synaptic Membranes / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D000871:Anthelmintics; D014151:Anti-Anxiety Agents; D002712:Chlorides; D007473:Ion Channels; D007783:Lactones; D011956:Receptors, Cell Surface; D011955:Receptors, Drug; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D005445:Flunitrazepam; C022120:avermectin B(1)a; D007559:Ivermectin; D001640:Bicuculline