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Keywords:

  • Neuronal nicotinic receptors;
  • Presynaptic nicotinic auto-receptor;
  • Hippocampal neurons;
  • Synaptosomes;
  • Xenopus oocytes;
  • Anatoxin-a;
  • Nicotine.

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.