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Imidazoline binding sites in human placenta: evidence for heterogeneity and a search for physiological function
Author(s) -
Diamant Sophia,
EldarGeva Talia,
Atlas Daphne
Publication year - 1992
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.1476-5381.1992.tb14300.x
Subject(s) - idazoxan , imidazoline receptor , syncytiotrophoblast , placenta , rauwolscine , receptor , chemistry , amiloride , medicine , endocrinology , binding site , biochemistry , biology , antagonist , yohimbine , prazosin , fetus , pregnancy , genetics , organic chemistry , sodium
1 An α 2 ‐adrenoceptor antagonist, idazoxan, that binds to both α 2 ‐adrenoceptors and to imidazoline sites (IR), has been used to characterize human placental IR. Human placenta is shown to be the richest source of IR (1800 ± 100 fmol mg −1 protein; K d 38.9 ± 3.4 n m ). 2 Primary cells derived from human placenta and grown in monolayers, also displayed a high density of receptors (3209 ± 136 fmol mg −1 in cytotrophoblasts and 3642 ± 144 fmol mg −1 protein in syncytiotrophoblast enriched cell culture). 3 [ 3 H]‐idazoxan did not show binding characteristics of α 2 ‐adrenoceptors in human placental membranes or human trophoblastic cells, thus making it a ligand of choice to study the imidazoline site. The tissue appeared to be lacking α 2 ‐adrenoceptors in that other α 2 ‐adrenoceptor ligands, [ 3 H]‐rauwolscine and [ 3 H]‐clonidine, do not bind to α 2 ‐adrenoceptors in human placenta. 4 IRs are localized on the cell surface, as determined by the release of bound [ 3 H]‐idazoxan from cells, when washed with high ionic/acidic medium. 5 Imidazoline receptors of human placenta display high affinity for amiloride (72 ± 27 n m ). The high affinity was used as a criterion to classify IR to IR a subtype (placenta, rabbit kidney, rabbit liver and rabbit adipose cells) as opposed to the IR b subtype which display low affinity for amiloride (> 2 μ m , in all the other tissues). 6 Several novel ligands comprising a guanido functional group attached to an aromatic residue (e.g. benziliden‐amino‐guanidine (BAG), guanido pyrole) display pronounced selectivity for IR over the α 2 ‐adrenoceptors as the affinity of BAG is about 40 fold higher ( K d = 18.9 ± 13.8 n m in human placenta), than the affinity for α 2 ‐adrenoceptors ( K d = 768 ± 299 n m in human platelets). Imidazoline sites bind selectively BAG and other guanido ligands thus indicating a distinct structural requirement at its site of binding. 7 K + channel blockers and monovalent ions (e.g. Cs + and NH 4 + ) interfere with idazoxan binding to IR, indicating a possible involvement of IR in K + transport.