Effects of acetylcholine and atropine on the bile flow and biliary excretion of digoxin in the isolated perfused rat liver.

The effects of acetylcholine (ACh). physostigmine, and atropine on bile flow and biliary elimination of digoxin were investigated using isolated rat liver perfusion. 1. ACh in the presence of physostigmine caused a temporary reduction in the bile secretion, while physostigmine alone had no effect on the bile flow. 2. The biliary concentration of radioactivity derived from 3H-digoxin was slightly decreased after an addition of physostigmine alone. This effect of physostigmine was not potentiated by ACh. 3. The addition of ACh decreased transiently the biliary elimination of digoxin, as a result of the reduced bile flow. 4. Atropine in the concentration range of 10(-6)-10(-5) M in the perfusion medium did not affect bile flow or biliary excretion of digoxin; repeated addition of atropine (2 X 2 X 10(-4) M) caused a choleresis lasting over the perfusion period. 5. This choleresis induced by atropine was associated with decreased concentration of tritium in the bile but slightly increased biliary elimination of total radioactivity. 6. The results allow us to draw the conclusion that ACh in the presence of physostigmine has an inhibitory action on bile flow and biliary elimination of digoxin in the isolated perfused rat liver.