The effects of cocaine and nicotine on amino acid transport across the human placental cotyledon perfused in vitro.
The inhibitory effects of cocaine and nicotine on placental amino acid transport, as a mechanism contributing to intrauterine growth restriction, were investigated in the in vitro placental perfusion model. Amino acids that represent substrates for known placental transporters were selected: alanine (system A), glutamine (system N), phenylalanine and valine (system l), and arginine (system y(+)). Amino acid accumulation on the fetal side was measured in the absence of cocaine or nicotine (n = 7) and in the presence of 1.2 microg/ml cocaine (n = 6), 120 ng/ml nicotine (n = 6), or both (n = 6). Neither cocaine nor nicotine alone significantly inhibited alanine transport, whereas their combination did (P =.02). Significant inhibition of arginine transport was detected with nicotine (P =.007), cocaine (P =.01), and their combination (P =.01), whereas phenylalanine (P =.03, P =.04) and valine (P =.03, P =.04) transport was affected by cocaine and the combination of cocaine and nicotine, respectively. For glutamine, neither cocaine, nicotine, nor their combination had a statistically significant inhibitory effect. In conclusion, both cocaine and nicotine may contribute to fetal growth restriction by interfering with the activity of amino acids transporters that are necessary to maintain the nutrient gradients associated with normal fetal growth.
Pastrakuljic
A
A
Division of Clinical Pharmacology and Toxicology, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
Derewlany
L O
LO
Knie
B
B
Koren
G
G
D000596:Amino Acids / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D005260:Female; D006801:Humans; D009538:Nicotine / Q000494:pharmacology*; D010477:Perfusion; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy
D000596:Amino Acids; D009538:Nicotine; D003042:Cocaine