(+)-Anatoxin-a Is a Potent Agonist at Neuronal Nicotinic Acetylcholine Receptors
Article first published online: 5 OCT 2006
Journal of Neurochemistry
Volume 60, Issue 6, pages 2308–2311, June 1993
How to Cite
Thomas, P., Stephens, M., Wilkie, G., Amar, M., Lunt, G. G., Whiting, P., Gallagher, T., Pereira, E., Alkondon, M., Albuquerque, E. X. and Wonnacott, S. (1993), (+)-Anatoxin-a Is a Potent Agonist at Neuronal Nicotinic Acetylcholine Receptors. Journal of Neurochemistry, 60: 2308–2311. doi: 10.1111/j.1471-4159.1993.tb03519.x
- Issue published online: 5 OCT 2006
- Article first published online: 5 OCT 2006
- Resubmitted manuscript received February 12, 1993; accepted February 16, 1993.
- Neuronal nicotinic receptors;
- Presynaptic nicotinic auto-receptor;
- Hippocampal neurons;
- Xenopus oocytes;
Abstract: 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 α4 and β2 subunits. A presynaptic nicotinic receptor mediating acetylcholine release from hippocampal synaptosomes was similarly sensitive to (+)-anatoxin-a (EC50= 140 nM). α-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 γM, whereas α7 homooligomers reconstituted in Xenopus oocytes yielded an EC50 value of 0.58 γM for (+)-anatoxin-a. In these diverse preparations, (+)-anatoxin-a was between three and 50 times more potent than (–)-nicotine and ˜20 times more potent than acetylcholine, making it the most efficacious nicotinic agonist thus far described.