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ARS Home » Pacific West Area » Logan, Utah » Poisonous Plant Research » Research » Publications at this Location » Publication #320872
Title: The non-competitive blockade of GABAA receptors by an aqueous extract of water hemlock (Cicuta douglassi) tubers

Author
item Green, Benedict - Ben
item GOULART, CAMILA - Rio Grande Do Sul State Department Of Agricultural Research
item Welch, Kevin
item Pfister, James
item McCollum, Isabelle - Anita
item Gardner, Dale

Submitted to: Toxicon
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/14/2015
Publication Date: 10/3/2015
Publication URL: http://handle.nal.usda.gov/10113/62893
Citation: Green, B.T., Goulart, C., Welch, K.D., Pfister, J.A., Mccollum, I.J., Gardner, D.R. 2015. The non-competitive blockade of GABAA receptors by an aqueous extract of water hemlock (Cicuta douglassi) tubers. Toxicon. 108:11-14.

Interpretive Summary: The pharmacodynamic characterization of water hemlock (Cicuta spp.) is lacking, this research identifies the pharmacological mechanism of action of an extract from water hemlock. Moreover, we reverse the actions of the extract on a cultured cell line with midazolam, a benzodiazepine used in medicine.

Technical Abstract: Teratogenic alkaloids can cause developmental defects due to the inhibition of fetal movement from the desensitization of fetal muscle-type nicotinic acetylcholine receptors (nAChR). In this study, we tested the hypothesis that the piperidine alkaloid anabaseine a 1,2-dehydropiperidine and anabasine, its 1,2 unsaturated analogue desensitize nAChRs expressed by TE-671 cells and SH-SY5Y cells. The cells were exposed to five concentrations of each alkaloid in log10molar increments from 10 nM to 100 uM and then to a fixed concentration of acetylcholine (ACh) (10 uM for SH-SY5Y cells and 1 uM for TE-671 cells) and the responses measured to assess receptor desensitization. The fifty percent desensitization response (DS50) was calculated from the ACh response. Epibatidine was the most potent desensitizer in both cell lines (DS50 = 0.09 and 0.3 uM in SH-SY5Y and TE-671 cells respectively). Anabaseine was a more potent desensitizer anabasine in both cell lines (DS50 values of 2.4 and 1.0 uM in SH-SY5Y and TE-671 cells respectively for anabasine and DS50 values of 5.6 and 2.3 uM in SH-SY5Y and TE-671 cells respectively for anabasine). The results from these experiments suggest that response of the cells to the addition of ACh after the initial agonist exposure was dependent on the potency of the first agonist. These results suggest that anabaseine, may be more effective at desensitizing fetal muscle-type nAChR than anabasine and therefore, potentially more teratogenic.