Abstract
Piperidine alkaloids are found in many species of plants including Conium maculatum, Nicotiana spp., and Lupinus spp. A pharmacodynamic comparison was made of the alkaloids ammodendrine, anabasine, anabaseine, and coniine in; SH‐SY5Y cells which express autonomic‐type nicotinic acetylcholine receptors (nAChR), and in TE‐671 cells which express fetal muscle‐type nAChR. Both cell lines were cultured in DMEM supplemented with fetal bovine serum and penicillin/streptomycin. Membrane depolarization responses were measured by changes in fluorescence of a membrane potential‐sensitive dye. The alkaloids and their enantiomers were more effective in depolarizing TE‐671 cells relative to SH‐SY5Y cells. The rank order of potency in TE‐671 cells was: anabaseine > (+)‐anabasine > (−)‐anabasine > (±)‐anabasine > (−)‐coniine > (±)‐coniine > (+)‐coniine > (±)‐ammodendrine > (+)‐ammodendrine. The rank order potency in SH‐SY5Y cells was: anabaseine > (+)‐anabasine > (−)‐coniine > (+)‐coniine > (+)‐ammodendrine > (−)‐anabasine > (±)‐coniine > (±)‐anabasine > (−)‐ammodendrine. The actions of these alkaloids at nAChRs in both cell lines could be distinguished by their maximum effects in depolarizing cell membrane potential. It is possible that the mechanism behind the toxic potential of these compounds is the activation of muscle‐type nAChR followed by desensitization. Research supported by ARS‐USDA.
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