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Concentration‐Dependent Actions of Piperidine Alkaloids on the Inhibition of Fetal Movement in Day 40 Pregnant Goats and Comparison to Cell‐Based Models.
Author(s) -
Green Benedict,
Welch Kevin D.,
Lee Steve T.,
Kem William R.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.679.8
Subject(s) - anabasine , fetus , epibatidine , chemistry , piperidine , alkaloid , pharmacology , phencyclidine , endocrinology , medicine , nicotinic agonist , biology , pregnancy , stereochemistry , biochemistry , receptor , nicotinic acetylcholine receptor , nmda receptor , genetics
Anabasine and anabaseine are potent and effective agonists at nicotinic acetylcholine receptors (nAChR). Anabasine in livestock species is teratogenic and has been shown to cause developmental defects that include arthrogyrposis, kyposis, lordosis, scoliosis, and torticollis. We have postulated that these fetal defects are due to the complete and sustained inhibition of fetal movement. The purpose of this research was to determine if cell‐based predictions of teratogenicity from TE‐671 cell experiments translate to inhibition of fetal movement in a day 40 pregnant goat model. We hypothesized that anabasine, anabaseine, epibatidine, and DMPP which are potent and effective agonists atfetal muscle‐type nAChR expressed by TE‐671 cells, would be effective at completely inhibiting fetal movement in a goat model the putative mechanism of teratogenicity in livestock species. Pregnant goats were I.V. dosed with anabasine, anabaseine, epibatidine, DMPP, or saline control on gestation day 40 and the number of fetal movements were measured by ultrasound periodically for 8 hours. The experiment was designed to only briefly inhibit fetal movement(< 3 h) and as a result, no terata were observed in any of the kids from the pregnant does dosed with any of the compounds in this study. Anabasine, at a dose of 0.8 mg/kg, completely inhibited fetal movement for 1.5 hours after dosing, and its actions were dose‐dependent with an IC 50 value of 0.1 mg/kg. Anabaseine, epibatidine, and DMPP did not completely inhibit fetal movement in day 40 pregnant goats. The results from this experiment suggest that while experiments with TE‐671 cells provide valuable information and predictions of the actions of plant alkaloids on fetal movement, in vivo experiments are still required in order to determine the ability of an alkaloid to inhibit fetal movement in livestock species and to predict teratogenic potential. Support or Funding Information Funding provided by USDA ARS This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .