Placental norepinephrine transporter development in the ovine fetus.
The placenta has been shown to be a site of expression of several of the monoamine membrane uptake transporters. However, the development and relative contribution of transport-dependent mechanisms to placental catecholamine clearance in vivo have not been demonstrated. These studies were designed to determine the development of the placental norepinephrine transporter (NET) and the relative contribution of transport dependent mechanisms to whole body and placental catecholamine clearance. Norepinephrine clearance and production rate were determined in 122 +/- 1 day gestation chronically catheterized fetal sheep. Placental clearance was shown to account for over 40 per cent of total intrauterine clearance and, of the clearance in the placenta, nearly 50 per cent was uptake, transport-dependent as shown by specific pharmacologic blockade. NET transport expression was examined by measurement nisoxetine binding in placenta and compared with binding in the frontal cortex of fetal, newborn and adult animals. Nisoxetine is a selective ligand for the norepinephrine transporter. Nisoxetine binding was 20-fold greater in placenta than in frontal cortex. Placental transporter binding decreased modestly in between 99 days gestation and term (145 days) but did not change in frontal cortex. These results suggest that expression of the norepinephrine transporter in the placenta is associated with a significant capacity for neurotransmitter re-uptake in utero. Given the high fetal norepinephrine production rate, this capacity is important for fetal homeostasis. This site of transporter expression may be important in the pathogenesis of derangements in catecholamine production in the fetus and in the adverse effects on the fetus of drugs, such as cocaine, which block catecholamine re-uptake.
Bzoskie
I
I
Department of Pediatrics, Harbor-UCLA Medical Center, UCLA School of Medicine, USA.
Blount
I
I
Kashiwai
K
K
Humme
J
J
Padbury
J F
JF
D000818:Animals; D001665:Binding Sites; D001692:Biological Transport; D002352:Carrier Proteins / Q000096:biosynthesis*; D005260:Female; D005333:Fetus / Q000378:metabolism*; D005473:Fluoxetine / Q000031:analogs & derivatives / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D012756:Sheep; D027981:Symporters
D002352:Carrier Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D027981:Symporters; D005473:Fluoxetine; C011386:nisoxetine; D009638:Norepinephrine