ABSTRACT
I. Introduction ............................................................................................................... 162
II. Plasma Membrane Monoamine Transporters in the Placenta .................................. 162 A . Normal Placenta .................................................................................................. 162
I. Monoamine Transport across the Brush-Border Membrane ......................... 162 a. Serotonin ................................................................................................... 162 b. Catecholamines ......................................................................................... 163
2. Monoamine Transport across the Basal Membrane ...................................... 163 B. Choriocarcinoma Cells ....................................................................................... 164
1. Serotonin ........................................................................................................ 164 2. Catecholamines .............................................................................................. 164
III. Pharmacology of the Placental Monoamine Transporters ....................................... 164 A. Serotonin Transporter ......................................................................................... 164 B. Norepinephrine Transporter ................................................................................ 165
V. Structural Features of the Placental Serotonin Transporter ..................................... 166 A . Chemical Modification Studies .......................................................................... 166 B. Molecular Cloning .............................................................................................. 167 C. Partial Purification and Characterization ........................................................... 168
VI. Regulation of the Placental Serotonin Transporter .................................................. 168 A. Cyclic AMP ........................................................................................................ 168 B. Protein Kinase C ................................................................................................. 169 C. Calmodulin .......................................................................................................... 169
VII. Vesicular Monoamine Transporter in the Placenta .................................................. 169
VIII. Monoamine Metabolism in the Placenta .................................................................. 169
X. Pharmacological and Pathological Relevance of the Placental Monoamine Transporters .......................................................................................... 171
XI. Conclusion ................................................................................................................. 171
References ........................................................................................................................... 172
The physiological and pathological roles of biogenic monoamines (serotonin, norepinephrine, and dopamine) in the human placenta have received increasing attention in recent years. It has been known for a long time that the placenta has an enormous ability to metabolize these monoamines. Interestingly, this tissue lacks the enzymatic machinery to synthesize the monoamines endogenously. Recently, the trophoblast cells of the human placenta have been shown to express monoamine transport systems in the plasma membrane which enable the cells to actively transport these compounds from maternal and fetal circulations. The metabolic fate of the monoamines thus transported into the cells is not completely known, but it appears that there are no storage mechanisms available for these monoamines inside the trophoblast cells. It is very likely that enzymatic breakdown initiated by monoamine oxidase is the primary pathway responsible for the handling of monoamines by the trophoblast cells. Little is known about the receptors for these monoamines in trophoblast cells, and this is an area which obviously requires attention in the coming years. Even though our present knowledge on various aspects of metabolism and function of the monoamines in the placenta ·is far from complete, there is compelling evidence to suggest an important role for these bioactive compounds in the physiology and pathology of the placenta and hence in the growth and development of the fetus.
