The CNS toxin anatoxin-A interacts with α4β2-nicotinic acetylcholine receptors in human cortex

The interaction of the central nervous system toxin anatoxin-A with alpha 4 beta 2 nicotinic acetylcholine receptors in human cerebral cortex (n=4) was investigated using [H-3]cytisine as a radioligand probe. Anatoxin-A inhibited [H-3]cytisine binding with an inhibition constant of 1.5x10(-9)+0.3x10(-9) M which compares to inhibition constants of 1.7x10(-10)+/-0.7x10(-10) M and 6.2x10(-9)+/-2.0x10(-9) M for epibaditine and nicotine respectively. The clinically neuroactive compounds imipramine and clozapine lacked any activity at concentrations up to 1 mM. These data suggest that the algae toxin anatoxin-A is able to interact in acute subtoxic and naturally occurring concentrations with human alpha 4 beta 2-nicotinic acetylcholine receptors in vivo. A contributory role of cholinergic toxins may be considered in the pathogenesis of Alzheimer's dementia, in which cholinergic neurons of the nucleus basalis Meynert are more severely damaged than other brainstem neurons.