Piperidine and pyridine alkaloid actions at fetal muscle‐type nicotinic acetylcholine receptors

Abstract

Preventing the normal movement of a developing fetus can result in congenital contracture‐type defects such as those seen in crooked calf syndrome. The desensitization of fetal muscle‐type nicotinic acetylcholine receptors (nAChR) by piperidine and pyridine alkaloids in a developing fetus is one putative mechanism behind the inhibition of fetal movement in animals. In this study, we tested the piperidine alkaloids anabasine and lobeline as well as the pyridine alkaloid myosmine for agonist actions and sensitivity to alpha conotoxins EI and GI antagonism at fetal muscle‐type nAChR expressed by TE‐671 cells using a membrane potential sensing dye based system. The alkaloids acted as agonists in the cell culture experiments. Anabasine and myosmine were sensitive to alpha conotoxin GI, and conotoxins did not block the actions of lobeline. We also tested if these alkaloids can decrease fetal movement in 40 day pregnant goats, dosed IV. Anabasine at 0.8 mg/kg, lobeline at 4 mg/kg and myosmine at 5 mg/kg significantly reduced fetal movement after IV dosing. These results suggest that anabasine and myosmine are nAChR agonists and that the three alkaloids have the potential to reduce fetal movement in animals. This research was supported by USDA/ARS.