Fetal Muscle-Type Nicotinic Acetylcholine Receptor Activation in TE-671 Cells and Inhibition of Fetal Movement in a Day 40 Pregnant Goat Model by Optical Isomers of the Piperidine Alkaloid Coniine
| العنوان: | Fetal Muscle-Type Nicotinic Acetylcholine Receptor Activation in TE-671 Cells and Inhibition of Fetal Movement in a Day 40 Pregnant Goat Model by Optical Isomers of the Piperidine Alkaloid Coniine |
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| المؤلفون: | James A. Pfister, Kip E. Panter, Stephen T. Lee, Kevin D. Welch, Benedict T. Green |
| المصدر: | Journal of Pharmacology and Experimental Therapeutics. 344:295-307 |
| بيانات النشر: | American Society for Pharmacology & Experimental Therapeutics (ASPET), 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Agonist, medicine.drug_class, ved/biology.organism_classification_rank.species, Receptors, Nicotinic, Pharmacology, Cell Line, Nicotine, chemistry.chemical_compound, Alkaloids, Piperidines, Pregnancy, Cell Line, Tumor, medicine, Animals, Humans, Muscle, Skeletal, Receptor, Fetal Movement, Fetus, Dose-Response Relationship, Drug, ved/biology, Goats, Alkaloid, Conium maculatum, Stereoisomerism, Calcium Channel Blockers, Acetylcholine, Nicotinic acetylcholine receptor, Coniine, chemistry, Mandelic Acids, Molecular Medicine, Female, Conotoxins, Crystallization, medicine.drug |
| الوصف: | Coniine is an optically active toxic piperidine alkaloid and nicotinic acetylcholine receptor (nAChR) agonist found in poison hemlock (Conium maculatum L.). Coniine teratogenicity is hypothesized to be attributable to the binding, activation, and prolonged desensitization of fetal muscle-type nAChR, which results in the complete inhibition of fetal movement. However, pharmacological evidence of coniine actions at fetal muscle-type nAChR is lacking. The present study compared (-)-coniine, (+)-coniine, and nicotine for the ability to inhibit fetal movement in a day 40 pregnant goat model and in TE-671 cells that express fetal muscle-type nAChR. Furthermore, α-conotoxins (CTx) EI and GI were used to antagonize the actions of (+)- and (-)-coniine in TE-671 cells. (-)-Coniine was more effective at eliciting electrical changes in TE-671 cells and inhibiting fetal movement than was (+)-coniine, suggesting stereoselectivity by the receptor. The pyridine alkaloid nicotine did not inhibit fetal movement in a day 40 pregnant goat model, suggesting agonist specificity for the inhibition of fetal movement. Low concentrations of both CTxs potentiated the TE-671 cell response and higher concentrations of CTx EI, and GI antagonized the actions of both coniine enantiomers demonstrating concentration-dependent coagonism and selective antagonism. These results provide pharmacological evidence that the piperidine alkaloid coniine is acting at fetal muscle-type nAChR in a concentration-dependent manner. |
| تدمد: | 1521-0103 0022-3565 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7a02e8f036d81d12f68423740454b33cTest https://doi.org/10.1124/jpet.112.199588Test |
| رقم الانضمام: | edsair.doi.dedup.....7a02e8f036d81d12f68423740454b33c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15210103 00223565 |
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