The effect of choline acetyltransferase inhibition on acetylcholine synthesis and release in term human placenta

The synthesis and release of acetylcholine (ACh) was studied in term human placental villous mince in vitro. During a 140-min incubation the placental tissue synthesized ACh at a rate of 2.59 nmol/g/min and released ACh into the medium at a rate of 0.78 nmol/g/min. Consequently there was an increase in tissue levels of ACh from an initial value of 83 to 321 nmol/g. Inhibition of choline acetyltransferase by 2-benzoylethyl trimethylammonium or 4-(1-naphthylvinyl)pyridine depressed the synthesis of ACh by over 75% and blocked the increase in tissue levels of ACh. The IC50 values for the inhibition of ACh synthesis and decrease in tissue levels were close to the IC50 values determined for inhibition of choline acetyltransferase in situ. Neither 2-benzoylethyl trimethylammonium nor 4-(1-naphthylvinyl)pyridine caused a significant effect on ACh release. 2-benzoylethyl trimethylammonium and 4-(1-naphthylvinyl)pyridine were quite effective in inhibiting the uptake of the neutral amino acid, alpha-aminoisobutyric acid, into the tissue. The inhibition of alpha-aminoisobutyric acid uptake paralleled the inhibition of ACh synthesis. These results support the hypothesis of an association between placental cholinergic activity and amino acid transport in the human placenta.