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ARS Home » Pacific West Area » Logan, Utah » Poisonous Plant Research » Research » Publications at this Location » Publication #332168
Title: Agonist mediated fetal muscle-type nicotinic acetylcholine receptor desensitization

Author
item Green, Benedict - Ben
item Lee, Stephen
item Welch, Kevin
item Panter, Kip
item McCollum, Isabelle - Anita

Submitted to: International Symposium on Poisonous Plants
Publication Type: Proceedings
Publication Acceptance Date: 5/28/2015
Publication Date: 6/5/2015
Citation: Green, B.T., Lee, S.T., Welch, K.D., Panter, K.E., Mccollum, I.J. 2015. Agonist mediated fetal muscle-type nicotinic acetylcholine receptor desensitization. International Symposium on Poisonous Plants. 9:296-300.

Interpretive Summary: The exposure of a fetus to teratogenic alkaloids from plants causes developmental defects in livestock due to the inhibition of fetal movement by alkaloids. The mechanism behind the inhibition of fetal movement is the desensitization of fetal muscle-type nicotinic acetylcholine receptors. In this study, we tested the hypothesis that that acetylcholine will be a more effective desensitizer of fetal muscle-type nAChR expressed in TE-671 cells than nicotine. In this work we confirm that acetylcholine is more effective at desensitizing than nicotine and that more research is needed on the mechanism behind the coniine induced inhibition of fetal movement in vivo.

Technical Abstract: The exposure of a developing embryo or fetus to teratogenic alkaloids from plants has the potential to cause developmental defects in livestock due to the inhibition of fetal movement by alkaloids. The mechanism behind the inhibition of fetal movement is the desensitization of fetal muscle-type nicotinic acetylcholine receptors (nAChR). In this study, we tested the hypothesis that that acetylcholine will be a more effective desensitizer of fetal muscle-type nAChR expressed in TE-671 cells than nicotine. The cell-based experiments were conducted using a membrane potential sensing dye-based system and a two-step agonist addition protocol with the second addition of agonist one log greater in concentration than the first. Treatment of the TE-671 cells with 10 µM ACh reduced the subsequent dye response of the cells to 100 µM ACh by 72%. The sequential dye responses to nicotine and coniine were only reduced at 1 mM which was most likely due blockade of the nAChR ion channel by the agonist. These results confirm that acetylcholine is more effective at desensitizing nAChR than nicotine and that more research is needed on the mechanism behind the coniine induced inhibition of fetal movement in vivo.