Relationship between [I-125]RTI-55-labeled cocaine binding sites and the serotonin transporter in rat placenta

We investigated the characteristics of cocainelike binding sites in rat pla centa using [I-125]RTI- 55. [H-3]paroxetine binding and immunocytochemical staining for serotonin [5-hydroxytryptamine (5-HT)] and for the 5-HT transp orter were also used to obtain evidence for rat placental 5-HT uptake. [I-1 25]RTI-55 saturation analyses with membranes from normal gestational day 20 placentas yielded curvilinear Scatchard plots that were resolved into high - and low-affinity components (mean dissociation constants of 0.29 and 7.9 nM, respectively). Drug competition studies with various monoamine uptake i nhibitors gave rise to complex multiphasic displacement curves, although th e results obtained with the selective 5-HT uptake inhibitor citalopram sugg est that the 5-HT transporter is an important component of placental high-a ffinity [I-125]RTI-55 binding. The presence of a rat placental 5-HT uptake system was-additionally supported by the [H-3]paroxetine binding experiment s and by the presence throughout the placenta of immunoreactivity for 5-HT and the 5-HT transporter. Immunostaining with both antibodies was most inte nse in the junctional zone, whereas the density of [I-125]RTI-55 binding si tes was greater in the placental labyrinth. This discrepancy may be due to the fact that [I-125]RTI-55 appears to be labeling additional cellular comp onents besides the 5-HT transporter. The presence of cocaine- and antidepre ssant-sensitive 5-HT transporters in the placenta has important implication s for the possible effects of these compounds on pregnancy and fetal develo pment.