[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.
Yao
Y
Y
Shanghai Institute of Physiology, Academia Sinica.
Li
Y
Y
D000818:Animals; D001231:Aspergillus flavus; D002642:Chick Embryo; D003001:Cloning, Molecular; D015870:Gene Expression; D007211:Indoles / Q000494:pharmacology*; D009183:Mycotoxins / Q000494:pharmacology*; D009865:Oocytes / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D011963:Receptors, GABA-A / Q000187:drug effects*; D014982:Xenopus laevis
D007211:Indoles; D009183:Mycotoxins; D012333:RNA, Messenger; D011963:Receptors, GABA-A; C073023:dihydroxyaflavinine