NOREPINEPHRINE TRANSPORTERS IN RAT PLACENTA LABELED WITH [H-3]NISOXETINE

Previous research has identified a norepinephrine (NE) transporter in brush-border membranes from human placental syncytiotrophoblastic cell s. In the present study, we used the selective ligand [H-3]nisoxetine to demonstrate the presence of an NE transporter in rat placental memb ranes, determine the binding characteristics of the transporter and as certain its localization by means of in vitro film and dry-emulsion au toradiography. Additional membrane binding studies were performed with [H-3]GBR 12935 to determine whether a dopamine transporter also was p resent in rat placenta. Saturation analyses carried out on washed memb rane fractions from whole rat placentas at gestational day 20 showed s aturable [H-3]nisoxetine binding (mean K-d = 1.00 nM, B-max = 1.24 pmo l/mg of protein) but no saturable binding of [H-3]GBR 12935. When vari ous monoamine uptake inhibitors were tested for their potency to inhib it placental [H-3]nisoxetine binding, the results supported the conclu sion that the radioligand was labeling an NE transporter. Autoradiogra phic studies showed the presence of [H-3]nisoxetine binding in all thr ee cellular zones of the rat placenta: the decidua, junctional zone an d labyrinth. Binding was greatest in the junctional zone, particularly in the giant trophoblastic cells. These findings indicate the presenc e of a high density of NE transporters in the late-gestation rat place nta. Catecholamine uptake probably has a multifunctional role in place ntal physiology, and blockade of the NE transporter by certain drugs s uch as cocaine may therefore contribute to the adverse effects of such compounds on pregnancy outcome and offspring development.