Investigation of the rate-limiting step in the synthesis of acetylcholine by the human placenta.
The uptake of [3H]choline and its conversion to [3H]acetylcholine were investigated in term human placental tissue in vitro. Although the net uptake of [3H]choline increased throughout a 45 min incubation period, intracellular [3H]choline levels reach a plateau after 2 min. There was a constant increase in [3H]acetylcholine levels throughout the incubation period. After 45 min, 36.5 per cent of the total intracellular tritium was recovered as acetylcholine by high-voltage electrophoresis. The effects of the choline acetyltransferase inhibitors, 2-benzoylethyltrimethyl-ammonium chloride (BETA) and 4-naphthylvinyl pyridine (NVP), and an inhibitor of choline uptake, hemicholinium-3 (HC-3), were also investigated for their influence on the uptake and metabolism of [3H]choline. A significant depression in both [3H]choline uptake and [3H]acetylcholine synthesis could be demonstrated with all three compounds, although with somewhat different time courses and activities. An analysis of the accumulation of [3H]acetylcholine in relation to the uptake and intracellular levels of [3H]choline as well as the patterns of inhibition produced by the inhibitors indicates that, unlike nervous tissue, the rate-limiting step in the synthesis of acetylcholine in human placental tissue is the transacetylation reaction catalysed by choline acetyltransferase.
D000109:Acetylcholine / Q000031:analogs & derivatives / Q000096:biosynthesis* / Q000494:pharmacology; D002794:Choline / Q000378:metabolism; D005260:Female; D006801:Humans; D007700:Kinetics; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy
C017058:(2-benzoylethyl)trimethylammonium; D002794:Choline; D000109:Acetylcholine