霉菌毒素Dihydroxyaflavinine非竞争性...

Fungal toxin dihydroxyaflavinine inhibits non-competitively GABAA receptor channel expressed in Xenopus oocytes]

Dihydroxyaflavinine is an indole-derived metabolite of Aspergillus flavus. Its action on GABA-induced response was quantitatively studied on the GABAA receptor expressed in Xenopus oocytes after injection of chick brain mRNA under voltage-clamp conditions. Dihydroxyaflavinine inhibits GABA-induced current non-competitively with KI = 12 mumol/L. This blockage is rapidly reversible. In comparison, the inhibitory effect of penicillin on GABAA receptor is enhanced by increasing GABA concentration. Ro 15-1788 (a benzodiazepine ligand with KD = 0.6--2 nmol/L) of concentration as high as 1 mumol/L, does not mask the action of 10 mumol/L dihydroxyaflavinine, indicating that dihydroxyaflavinine acts on a site different from benzodiazepines. Dihydroxyaflavinine appears to expedite desensitization of the receptor, which is similar to the action of picrotoxin and in contrast with that of penicillin and bicuculline.