(+)-Anatoxin-a is a potent agonist at neuronal nicotinic acetylcholine receptors.
The effects of the nicotinic agonist (+)-anatoxin-a have been examined in four different preparations, representing at least two classes of neuronal nicotinic receptors. (+)-Anatoxin-a was most potent (EC50 = 48 nM) in stimulating 86Rb+ influx into M10 cells, which express the nicotinic receptor subtype comprising alpha 4 and beta 2 subunits. A presynaptic nicotinic receptor mediating acetylcholine release from hippocampal synaptosomes was similarly sensitive to (+)-anatoxin-a (EC50 = 140 nM). alpha-Bungarotoxin-sensitive neuronal nicotinic receptors, studied using patch-clamp recording techniques, required slightly higher concentrations of this alkaloid for activation: Nicotinic currents in hippocampal neurons were activated by (+)-anatoxin-a with an EC50 of 3.9 microM, whereas alpha 7 homooligomers reconstituted in Xenopus oocytes yielded an EC50 value of 0.58 microM for (+)-anatoxin-a. In these diverse preparations, (+)-anatoxin-a was between three and 50 times more potent than (-)-nicotine and approximately 20 times more potent than acetylcholine, making it the most efficacious nicotinic agonist thus far described.
Thomas
P
P
Department of Biochemistry, University of Bath, England.
Stephens
M
M
Wilkie
G
G
Amar
M
M
Lunt
G G
GG
Whiting
P
P
Gallagher
T
T
Pereira
E
E
Alkondon
M
M
Albuquerque
E X
EX
D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology*; D002645:Chickens; D002794:Choline / Q000378:metabolism; D000087522:Cyanobacteria Toxins; D006624:Hippocampus / Q000378:metabolism*; D008387:Marine Toxins / Q000494:pharmacology*; D051379:Mice; D052998:Microcystins; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D011994:Recombinant Proteins / Q000187:drug effects / Q000378:metabolism; D012413:Rubidium / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D014162:Transfection; D014326:Tropanes; D014981:Xenopus
D001427:Bacterial Toxins; D000087522:Cyanobacteria Toxins; D008387:Marine Toxins; D052998:Microcystins; D011978:Receptors, Nicotinic; D011994:Recombinant Proteins; D014326:Tropanes; D009538:Nicotine; C509783:anatoxin a; D012413:Rubidium; D002794:Choline; D000109:Acetylcholine