1. Academic Validation
  2. (+)-Anatoxin-a is a potent agonist at neuronal nicotinic acetylcholine receptors

(+)-Anatoxin-a is a potent agonist at neuronal nicotinic acetylcholine receptors

  • J Neurochem. 1993 Jun;60(6):2308-11. doi: 10.1111/j.1471-4159.1993.tb03519.x.
P Thomas 1 M Stephens G Wilkie M Amar G G Lunt P Whiting T Gallagher E Pereira M Alkondon E X Albuquerque, et al.
Affiliations

Affiliation

  • 1 Department of Biochemistry, University of Bath, England.
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 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.

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