Inhibition of the uptake of amino acids in human placental villus by nicotine, cocaine and morphine

Nicotine, morphine and cocaine cause intrauterine fetal growth retardation. Insufficiency of amino acid (AA) transport across placenta in the presence of these drugs may contribute to fetal growth retardation. Therefore, the effects of these drugs on the active uptake of various ¹⁴C-labeled AA were studied in isolated human placental villus. Uptake of the AA was determined either by measuring the decline in AA in the medium or the accumulation of AA within the tissue. The uptake of the neutral AA, α-aminoisobutyric acid (AIB), was depressed in a dose-response fashion by millimolar concentrations of nicotine, morphine and cocaine. The inhibition of AIB uptake by these drugs was not competitive. The uptake of L-lysine was inhibited 30% by nicotine. The uptake of isoleucine was inhibited more than 30% by nicotine (5 mM), cocaine (3.5 mM) and morphine (2 mM). The intracellular levels of L-tryptophan and cycloleucine did not exceed their concentration in the medium (0.1 mM) and were not altered by these drugs. These findings suggest the transport processes for different classes of AA are subject to differential inhibition by specific agents. They also indicate that the fetal amino acid pools may be altered in the presence of these drugs which can contribute to its retarded growth.