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Differential localization of endothelin ET a and ET B binding sites in human placenta
Author(s) -
Rutherford Richard A.D.,
Wharton John,
McCarthy Andrew,
Gordon Lee,
Sullivan Mark H.F.,
Elder Murdoch G.,
Polak Julia M.
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13605.x
Subject(s) - endothelin receptor , placenta , receptor , endocrinology , biology , endothelin 1 , medicine , decidua , population , microbiology and biotechnology , binding site , chemistry , fetus , biochemistry , pregnancy , genetics , environmental health
1 The localization and differential distribution of endothelin (ET) receptor subtypes (ET A and ET B ) was investigated in sections of human placenta by use of quantitative in vitro autoradiography and receptor selective ligands. 2 Specific, high density [ 125 I]‐ET‐1 binding sites were localized to the decidua and foetal membranes as well as to arteries and veins in the chorionic plate and throughout the villous tree. Moderate to low density binding was found in the extravillous and villous trophoblast respectively. 3 [ 125 I]‐ET‐1 binding sites exhibited a rank order of inhibition by unlabelled peptide sequences (ET‐1 > ET‐3 >[Ala 3,11,18 Nle 7 ]‐ET‐1 > BQ123 ≥ sarafotoxin 6c). However, in contrast to the monophasic inhibition curve of ET‐1, the other sequences produced a significantly better fit to a two component inhibition curve suggesting the presence of a heterogeneous population of ET binding sites. 4 ET A and ET B receptors were distinguished by competitive inhibition of [ 125 I]‐ET‐1 binding with increasing concentrations of unlabelled ET‐3, [Ala 3,11,18 Nle 7 ]‐ET‐1, sarafotoxin 6c and BQ123 and by incubating sections with the ET B agonist, [ 125 I]‐BQ3020. ET receptor subtypes exhibited a differential distribution in the placenta. ET A type binding sites predominated (∼ 80% of the total) on veins and arteries in the chorionic plate. Veins in stem villi, blood vessels in distal regions of the villous tree and decidual cells displayed a high density (∼ 60–70% of the total) of the ET B receptor subtype. 5 No difference was detected in either the relative density of [ 125 I]‐ET‐1 binding sites or the proportion of ET A to ET B sites in placentae from pregnancies complicated by pre‐eclampsia compared with normal term controls. 6 ET may have a local autocrine or paracrine role in the placenta, acting via specific receptors to influence foetoplacental blood flow and other aspects of placental function.