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United States Department of Agriculture

Agricultural Research Service

Research Project: POISONING OF LIVESTOCK BY VARIOUS LARKSPUR SPECIES (DELPHINIUM)

Location: Poisonous Plant Research

Title: Potentiation of the actions of acetylcholine, epibatidine, and nicotine by methyllycaconitine at fetal muscle-type nicotinic acetylcholine receptors

Authors
item Green, Benedict
item Welch, Kevin
item Cook, Daniel
item Gardner, Dale

Submitted to: European Journal of Pharmacology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: April 18, 2011
Publication Date: July 15, 2011
Citation: Green, B.T., Welch, K.D., Cook, D., Gardner, D.R. 2011. Potentiation of the actions of acetylcholine, epibatidine, and nicotine by methyllycaconitine at fetal muscle-type nicotinic acetylcholine receptors. European Journal of Pharmacology. 662(1-3):15-21.

Interpretive Summary: Toxic alkaloids from larkspur species cause muscle weakness in cattle. One alkaloid in particular, MLA, is found in high concentrations in toxic larkspur. This alkaloid is a potent and selective blocker of neuronal nicotinic acetylcholine receptors. This study characterized the affects of the blocker MLA on the actions of three nicotinic acetylcholine receptor agonists. These effects were assessed by measuring changes in membrane potential sensing dye responses of TE-671 cells. Changes in cell membrane potential from the addition of agonists were measured as changes in fluorescence of a membrane potential-sensitive dye. MLA alone was without effect. MLA at low concentrations potentiated the response of TE-671 cells to acetylcholine, epibatidine, nicotine, and neostigmine. The amount of potentiation was agonist-dependant as well as concentration-dependant. These results suggest that the poisoning of cattle by norditerpenoid alkaloids found in larkspur may be more complex than previously thought.

Technical Abstract: Norditerpenoid alkaloids from Delphinium spp. (larkspur) have been described as possessing “curariform-like” activity in cattle and are of economic importance because of the poisonings they cause. Methyllycaconitine (MLA) is a norditerpenoid alkaloid found in high abundance in toxic larkspur, and is a potent and selective antagonist of a7-nicotinic acetylcholine receptors. The aim of this study was to characterize the affects of MLA on the actions of three nicotinic acetylcholine receptor agonists acetylcholine, epibatidine, nicotine, and the anticholinesterase agent neostigmine. These effects were assessed by measuring changes in membrane potential sensing dye responses of TE-671 cells expressing (a1)2ß1'd nicotinic acetylcholine receptors. Changes in cell membrane potential from the addition of agonists were measured as changes in fluorescence of a membrane potential-sensitive dye and normalized to the maximum epibatidine response. MLA in the absence of agonist was without effect. MLA at nanomolar concentrations potentiated the membrane potential sensing dye response of TE-671 cells to acetylcholine, epibatidine, nicotine, and neostigmine. The amount of potentiation was agonist-dependant as well as concentration-dependant. These results suggest that the poisoning of cattle by norditerpenoid alkaloids found in larkspur may be more complex than previously thought.

Last Modified: 4/17/2014
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