The expression and activity of monoamine oxidase A, but not of the serotonin transporter, is decreased in human placenta from pre-eclamptic pregnancies

Life Sci. 2000 Nov 3;67(24):2961-9. doi: 10.1016/s0024-3205(00)00883-3.

Abstract

Serotonin (5-HT) plays a pivotal role in pregnancy and a hyperserotonomic condition has been documented in pre-eclampsia. We have attempted to elucidate the possible participation of 5-HT as an aetiological factor in pre-eclampsia, by estimating the activity and expression of the 5-HT transporter (SERT) and monoamine oxidase A (MAO-A) in human placenta from full term normal (NG) and severe pre-eclamptic (PES) pregnancies. Uptake of 5-[1,2-3H] hydroxytryptamine binoxalate (specific radioactivity, 30.4 Ci/mmol) was determined in placental brush border vesicles by a rapid filtration technique. 5-HT metabolism in placental homogenate was measured using a HPLC-ECD system. Expression of SERT and MAO-A was determined by Western blot, using specific antibodies against the human SERT and MAO-A in placental tissues obtained from NG and PES. Our results, showed no significant difference in 5-HT uptake between both groups. However, 5-HT metabolism was significantly lower in placental homogenates from PES than in NG placentas, with the pathological preparations showing no MAO-A activity against 5-HT during the first 60 min of incubation (87% and 5% of metabolism of 5-HT initially added, NG and PES respectively). Western blot analysis showed a similar expression of SERT in BBMV from NG and PES. However, unlike for normal pregnancies, the expression of MAO-A in placental homogenates from PES was found to be very low, or almost negligible. These findings confirm our previous results and suggest that the higher plasma free 5-HT levels observed in severe pre-eclampsia could be mainly due to a reduction in placental MAO-A expression and activity and are not limited by the expression and uptake of 5-HT into the placental tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Carrier Proteins / metabolism*
  • Chromatography, High Pressure Liquid
  • Female
  • Humans
  • Membrane Glycoproteins / metabolism*
  • Membrane Transport Proteins*
  • Microvilli / metabolism
  • Monoamine Oxidase / metabolism*
  • Nerve Tissue Proteins*
  • Placenta / enzymology*
  • Pre-Eclampsia*
  • Pregnancy
  • Serotonin / metabolism*
  • Serotonin / pharmacokinetics
  • Serotonin Plasma Membrane Transport Proteins
  • Tritium

Substances

  • Carrier Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Tritium
  • Serotonin
  • Monoamine Oxidase