Human placental cholinergic system: depression of the uptake of alpha-aminoisobutyric acid in isolated human placental villi by choline acetyltransferase inhibitors

Abstract

(2-Benzoylethyl)trimethylammonium chloride (BETA), bromoacetylcholine and 4-(1-naphthylvinyl)pyridine are potent inhibitors of choline acetyltransferase (ChA). In order to evaluate the role of acetylcholine in human placenta, the effects of the above ChA inhibitors on the uptake of [alpha-14C]aminoisobutyric acid (AIB) by isolated human placental villi were studied. All three inhibitors were able to inhibit AIB uptake by the tissue. The ID50 for BETA, the most potent compound, was about 6.2 x 10(-5) M. The blockade of AIB uptake closely paralleled the potency for inhibition of ChA in a series of keto-analogs of acetylcholine related to BETA. There was a positive relationship between the blockade of AIB uptake and the inhibition of ChA by BETA in situ. Hemicholinium-3 had no significant effect on AIB uptake. The ChA inhibitors did not exhibit significant effects on cell viability as determined by tissue lactic dehydrogenase. These observations indicate that the uptake of neutral amino acids by human placental villus is linked to acetylcholine synthesis.