Comparison of nicotinic receptor binding and biotransformation of coniine in the rat and chick

Toxicology Letters
C S ForsythA A Frank

Abstract

Coniine, an alkaloid from Conium maculatum (poison hemlock), is a known teratogen in many domestic species with maternal ingestion resulting in arthrogryposis of the offspring. We have previously shown that rats are not susceptible and rabbits only weakly susceptible to coniine-induced arthrogryposis. However, the chick embryo does provide a reproducible laboratory animal model of coniine-induced teratogenesis. The reason for this cross-species variation is unknown. The purpose of this study was to evaluate coniine binding to nicotinic receptors and to measure coniine metabolism in vitro between susceptible and non-susceptible species. Using the chick model, neither the peripheral nicotinic receptor antagonist d-tubocurarine chloride nor the central nicotinic receptor antagonist trimethaphan camsylate blocked the teratogenesis or lethality of 1.5% coniine (50 microliters/egg). Trimethaphan camsylate enhanced coniine-induced lethality in a dose-dependent manner. Neither nicotinic receptor blocker prevented nicotine sulfate-induced malformations but d-tubocurarine chloride did block lethality in a dose-dependent manner. Competition by coniine for [125I]-alpha-bungarotoxin to nicotinic receptors isolated from adult rat diaphragm a...Continue Reading

References

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Citations

Mar 31, 2012·Toxicological Sciences : an Official Journal of the Society of Toxicology·Reza J RasoulpourRichard Billington
Jul 8, 2009·Journal of Ethnopharmacology·Okan ArihanMustafa Ilhan
May 17, 2014·Critical Reviews in Toxicology·Robert G Ellis-HutchingsRichard Billington
Apr 23, 2013·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Benedict T GreenKip E Panter
Nov 15, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hannu Hotti, Heiko Rischer
Jan 28, 2005·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Sem GeniniPeter Vögeli
Sep 4, 2008·Chemical Research in Toxicology·Stephen T LeeKip E Panter

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