REGIONAL DISTRIBUTION AND PHARMACOLOGICAL CHARACTERIZATION OF [I-125] ENDOTHELIN-1 BINDING-SITES IN HUMAN FETAL PLACENTAL VESSELS

High-ttfnity binding sites for [125I]endothelin(ET)-1 have been detected in purified membrane preparations of the fetal arteries and veins ofthe chorionic plate and the stem villi vessels of the human term placenta. Regardless of the vessel type, the apparent dissociation constant was found to be in the picomolar range (26 → 45 pM), and the Bmax value close to 600 fmol/mg protein. In stern villi vessels, ET-1, ET-2, sarafotoxin SO and vasocontractor intestinal peptide (VIC, were approximately equipotent in their competitive displacement of [125I]ET-1 binding. The endothelin precursors, human and porcine big-endothelin, recognized ET-1 sites with low affinity (nM range), a finding which reflects their low potency as recognized vasocontractant agents. Interestingly, [125I]ET-1 binding parameters and pharmacological profiles were identical in fetal veins and arteries of the chorionicplate. Similarly, a study carried out in rat chotic membranes, revealed the presence of high affinity [125I]ET-1 bindingsites with pharmacological characteristics close to those of the human stem villi vessels. In all vessels investigated, the bindingpattern of ET-3 against [125I]ET-1 was of a non-competitive nature. Thus, these results demonstrate the presence of specific [125I]ET-1 binding sites along the vascular tree of the fetal side of the placenta and would support evidence currently available, favouring the existence of distinct ET-1 and ET-3 receptors. Finally, ET-1 in the human placenta may play an important physiological role as regulator of vascular resistance and/or be implicated as a pathological factor in certain pregnancy-related diseases. © 1991.