Anatoxin-a-evoked [3H]dopamine release from rat striatal synaptosomes

Neuropharmacology. 1995 Nov;34(11):1535-41. doi: 10.1016/0028-3908(95)00122-m.


Presynaptic nicotinic acetylcholine receptors on striatal nerve terminals modulate the release of dopamine. Using rat striatal synaptosomes loaded with [3H]dopamine, we have characterized the action of the selective nicotinic agonist, (+/-)anatoxin-a, with respect to [3H]dopamine release, in order to explore the mechanisms coupling nicotinic receptor activation to exocytosis. Anatoxin-a evoked [3H]dopamine release in a concentration-dependent and mecamylamine-sensitive manner, EC50 = 0.11 microM. The maximum [3H]dopamine release elicited by anatoxin-a was only 20% of the maximum elicited by KCl depolarization; there was no additivity between anatoxin-a and sub-maximal concentrations of KCl. Both agents stimulated Ca(2+)-dependent release that was equally sensitive to inhibition by 200 microM Cd2+. This result suggests that anatoxin-a-stimulated exocytosis is mediated by Ca2+ influx via voltage-sensitive Ca2+ channels, with little contribution from Ca2+ entering directly through the nicotinic receptor channel. This view is supported by the abolition of anatoxin-a-evoked [3H]dopamine release in Na(+)-depleted medium. A partial (40%) inhibition by tetrodotoxin was observed. These data suggest that activation of presynaptic nicotinic acetylcholine receptors by anatoxin-a results in an influx of Na+, producing sufficient local depolarization to open voltage-sensitive Ca2+ and Na+ channels. The latter may then amplify the response, activating further Ca2+ channels. The particular voltage-sensitive Ca2+ channels involved remain to be determined.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Toxins / pharmacology*
  • Calcium / metabolism
  • Corpus Striatum / drug effects
  • Corpus Striatum / physiology*
  • Cyanobacteria*
  • Dopamine / metabolism
  • Dopamine / physiology*
  • Ion Channels / drug effects
  • Male
  • Marine Toxins / pharmacology*
  • Microcystins
  • Nicotinic Agonists / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Synaptosomes / drug effects
  • Synaptosomes / physiology*
  • Tropanes


  • Bacterial Toxins
  • Ion Channels
  • Marine Toxins
  • Microcystins
  • Nicotinic Agonists
  • Tropanes
  • cyanobacterial toxin
  • anatoxin a
  • Calcium
  • Dopamine