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United States Department of Agriculture

Agricultural Research Service

Research Project: LIVESTOCK LOSSES FROM ABORTIFACIENT AND TERATOGENIC PLANTS

Location: Poisonous Plant Research

Title: A pharmacodynamic comparison of piperidine and pyridine alkaloid actions at fetal muscle-type nicotinic acetylcholine receptors (nAChR)

Authors
item Green, Benedict
item Lee, Stephen
item Panter, Kip

Submitted to: Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: March 1, 2012
Publication Date: April 1, 2012
Repository URL: http://www.fasebj.org/cgi/content/meeting_abstract/26/1_MeetingAbstracts/1048.6?sid=1cc784b8-d338-4066-a439-c520fd715fad
Citation: Green, B.T., Lee, S.T., Panter, K.E. 2012. A pharmacodynamic comparison of piperidine and pyridine alkaloid actions at fetal muscle-type nicotinic acetylcholine receptors (nAChR). Experimental Biology. 26: 1048.6.

Interpretive Summary: Piperidine and pyridine alkaloids are found in many species of plants including Lobelia spp., Conium spp., Nicotiana spp., and Lupinus spp. Some of these alkaloids cause multiple congenital contracture deformities (MCC) and cleft palates in cattle, pigs, sheep, and goats. The mechanism behind MCC defect formation in livestock is thought to be the inhibition of fetal movement due to stimulation followed by desensitization of fetal muscle-type nAChR. A pharmacodynamic comparison of piperidine and pyridine alkaloids was made in TE-671 cells that express fetal muscle-type nAChR. TE-671 cells were cultured in DMEM supplemented with fetal bovine serum and penicillin/streptomycin. The membrane depolarization responses were measured by changes in fluorescence of a membrane potential-sensitive dye. Alkaloids with a carbon side-chain of at least three carbons or larger attached to the carbon alpha to the piperidine nitrogen were more potent and effective. The presence of a double bond adjacent to the nitrogen of the piperidine or pyridine ring increased potency. The rank order of potency was: anabasine > nicotine > coniine > lobeline > myosmine > ammodendrine. This research supported by ARS-USDA.

Technical Abstract: Piperidine and pyridine alkaloids are found in many species of plants including Lobelia spp., Conium spp., Nicotiana spp., and Lupinus spp. Some of these alkaloids cause multiple congenital contracture deformities (MCC) and cleft palates in cattle, pigs, sheep, and goats. The mechanism behind MCC defect formation in livestock is thought to be the inhibition of fetal movement due to stimulation followed by desensitization of fetal muscle-type nAChR. A pharmacodynamic comparison of piperidine and pyridine alkaloids was made in TE-671 cells that express fetal muscle-type nAChR. TE-671 cells were cultured in DMEM supplemented with fetal bovine serum and penicillin/streptomycin. The membrane depolarization responses were measured by changes in fluorescence of a membrane potential-sensitive dye. Alkaloids with a carbon side-chain of at least three carbons or larger attached to the carbon alpha to the piperidine nitrogen were more potent and effective. The presence of a double bond adjacent to the nitrogen of the piperidine or pyridine ring increased potency. The rank order of potency was: anabasine > nicotine > coniine > lobeline > myosmine > ammodendrine. This research supported by ARS-USDA.

Last Modified: 9/21/2014
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