Selective cytostatic and neurotoxic effects of avermectins and activation of the GABAalpha receptors.
A natural avermectin complex, aversectin C, was shown to be capable of exerting selective cytostatic and neurotoxic effects on mammalian cells. Specifically, it killed proliferating neuroblastoma B103 cells but was non-toxic for differentiated cells of this culture. The antiproliferation action of aversectin C was not inhibited by bicuculline or picrotoxin, antagonists of the GABAalpha receptors, and was partly due to the action of avermectin A1, a component of aversectin C. Aversectin C irreversibly suppressed activity of 60% neurons in medial septal slices of the rat brain. More than 55% of them were the GABAalpha- and B1-sensitive neurons whereas the rest, about 45% neurons, were the GABAalpha-insensitive and the neurotoxic effect of aversectin C was caused mainly by the B2 component.
Kokoz
Y M
YM
Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Moscow Region. kokoz@venus.iteb.serpukhov.su
Tsyganova
V G
VG
Korystova
A F
AF
Grichenko
A S
AS
Zenchenko
K I
KI
Drinyaev
V A
VA
Mosin
V A
VA
Kruglyak
E B
EB
Sterlina
T S
TS
Victorov
A V
AV
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D007559:Ivermectin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009447:Neuroblastoma / Q000188:drug therapy; D009474:Neurons / Q000187:drug effects*; D009498:Neurotoxins / Q000494:pharmacology*; D010424:Pentobarbital / Q000494:pharmacology; D010852:Picrotoxin; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects*; D012686:Septal Nuclei / Q000187:drug effects; D014407:Tumor Cells, Cultured
D001640:Bicuculline; D018755:GABA Agonists; D018756:GABA Antagonists; D007559:Ivermectin; D009498:Neurotoxins; D010424:Pentobarbital; D010852:Picrotoxin; D011963:Receptors, GABA-A; C048324:abamectin; C019264:avermectin