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Identification of human platelet a 2 ‐adrenoceptors with a new antagonist [ 3 H]‐RX821002, a 2‐methoxy derivative of idazoxan
Author(s) -
Galitzky Jean,
Senard Jean Michel,
Lafontan Max,
Stillings Mike,
Montastruc Jean Louis,
Berlan Michel
Publication year - 1990
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.1476-5381.1990.tb14105.x
Subject(s) - yohimbine , chemistry , oxymetazoline , prazosin , imidazoline receptor , idazoxan , antagonist , radioligand assay , stereochemistry , adrenergic receptor , endocrinology , binding site , receptor , biochemistry , biology
1 The binding of a new α 2 ‐adrenoceptor antagonist, [ 3 H]‐RX821002 (2‐(2‐methoxy‐l,4‐benzodioxan‐2‐yl)‐2‐imidazoline), was investigated in human platelet membranes and compared with [ 3 H]‐yohimbine binding parameters. 2 Analysis of kinetic data revealed association and dissociation time courses consistent with a simple bimolecular reaction. Saturation isotherms showed that [ 3 H]‐RX821002 labelled a higher total number of α 2 ‐binding sites (224 ± 31 vs 168 ± 24 fmol mg −1 protein) than [ 3 H]‐yohimbine and with higher affinity ( K d : 0.92 ± 0.06 vs 1.51 ± 0.08n m ). Moreover [ 3 H]‐RX821002 exhibited a lower percentage of nonspecific binding. 3 The difference in total binding is due to a better labelling of the α 2 ‐adrenoceptors in the low affinity state by [ 3 H]‐RX821002 since the labelled receptors number in high affinity state was identical with the two radioligands. 4 [ 3 H]‐RX821002 binding displayed a specificity similar to that obtained with [ 3 H]‐yohimbine. The potency of various compounds acting on adrenoceptors was: yohimbine > oxymetazoline > UK 14304 > (−)−adrenaline > prazosin ≥ (+)‐adrenaline > isoprenaline. This order of potency is classical for an α 2A ‐adrenoceptor. 5 RX821002 is a more potent α 2 ‐adrenoceptor antagonist than yohimbine on adrenaline‐induced platelet aggregation. 6 These results indicate that [ 3 H]‐RX821002 is a suitable ligand for the identification of human platelet α 2 ‐adrenoceptors.