Action of tremorgenic mycotoxins on GABAA receptor.
The effects of four tremorgenic and one nontremorgenic mycotoxins were studied on gamma-aminobutyric acid (GABAA) receptor binding and function in rat brain and on binding of a voltage-operated Cl- channel in Torpedo electric organ. None of the mycotoxins had significant effect on [3H]muscimol or [3H]flunitrazepam binding to the GABAA receptor. However, only the four tremorgenic mycotoxins inhibited GABA-induced 36Cl- influx and [35S] t-butylbicyclophosphorothionate [( 35S]TBPS) binding in rat brain membranes, while the nontremorgenic verruculotoxin had no effect. Inhibition of [35S]TBPS binding by paspalinine was non-competitive. This suggests that tremorgenic mycotoxins inhibit GABAA receptor function by binding close to the receptor's Cl- channel. On the voltage-operated Cl- channel, only high concentrations of verruculogen and verruculotoxin caused significant inhibition of the channel's binding of [35S]TBPS. The data suggest that the tremorgenic action of these mycotoxins may be due in part to their inhibition of GABAA receptor function.
D000818:Animals; D001921:Brain / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002712:Chlorides / Q000378:metabolism; D004557:Electric Organ / Q000378:metabolism; D005445:Flunitrazepam / Q000378:metabolism; D066298:In Vitro Techniques; D007473:Ion Channels / Q000378:metabolism; D008297:Male; D009118:Muscimol / Q000378:metabolism; D009183:Mycotoxins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D014101:Torpedo; D014202:Tremor / Q000139:chemically induced*
D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002712:Chlorides; D007473:Ion Channels; D009183:Mycotoxins; D011963:Receptors, GABA-A; D009118:Muscimol; D005445:Flunitrazepam; C037476:tert-butylbicyclophosphorothionate