Acetylcholinesterase and butyrylcholinesterase activity in the human term placenta: implications for fetal cocaine exposure.
The characterization of the enzymes responsible for drug metabolism in the human placenta is of great importance in determining the possible role the placenta plays in protecting the fetus from potentially fetotoxic drugs. We speculate that the placenta metabolizes cocaine, serving to protect the fetus from the drug's ill effects. Cholinesterase, the principle enzyme that metabolizes cocaine, has been hypothesized to be present yet is not well characterized in the human placenta. The purpose of this study was to quantify human placental acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity. Human placentas were obtained from elective cesarean sections, and several lobules were thoroughly perfused with cold buffer to ensure minimal contamination from erythrocyte AChE. Subcellular fractions were then prepared from these lobules by using standard differential centrifugation techniques. Microsomes and cytosol were assayed for AChE and BChE activity by using a spectrophotometric assay. BChE activity was found in the cytosolic fraction of the placental villous tissue, whereas AChE activity was measured in the microsomal fraction. By demonstrating that BChE activity is present in human term placenta we have shown that this organ has the capacity to metabolize cocaine and may therefore serve as a metabolic barrier to fetal exposure to cocaine.
Simone
C
C
Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, Toronto, Ontario, Canada.
Derewlany
L O
LO
Oskamp
M
M
Johnson
D
D
Knie
B
B
Koren
G
G
D000110:Acetylcholinesterase / Q000378:metabolism*; D001711:Biotransformation; D002091:Butyrylcholinesterase / Q000378:metabolism*; D003042:Cocaine / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D005333:Fetus / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D010920:Placenta / Q000201:enzymology* / Q000378:metabolism; D011247:Pregnancy; D013347:Subcellular Fractions / Q000201:enzymology
D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D003042:Cocaine