LOW-AFFINITY CONDITIONS FOR AGONISTS INCREASE THE BINDING OF THE ANTAGONIST [H-3] RX821002 TO THE ALPHA (2B-C)-ADRENOCEPTOR SUBTYPES IN HUMAN BRAIN AND RAT-KIDNEY/

The mixture of 5'-guanylylimidodiphosphate (Gpp(NH)p)/EDTA/NaCl has be en used to delineate low-affinity conditions for agonists binding to G -protein-linked receptors. The effects of this mixture on [H-3]RX82100 2 (2-methoxyidazoxan) binding to alpha(2)-adrenoceptors were evaluated in different tissues. The density of alpha(2)-adrenoceptors in the pr esence of the mixture was 11, 78 and 60% higher in human cortex (predo minant alpha(2A)), human caudate (alpha(2A) + alpha(2C)) and rat kidne y (alpha(2A) + alpha(2B)), respectively, than in its absence. In rat k idney, masking of alpha(2B)-adrenoceptors by ARC239 ]-ethyl]-4,4-dimet hyl-1,3-(2H,4H-isoquinolindione) (50 nM) or masking of alpha(2A)-adren oceptors by BRL44408 1,3-dihydroisoindole)methyl]-4,5-dihydroimidazole ) (100 nM) demonstrated that the increase was in the alpha(2B)-adrenoc eptor but not in the alpha(2A)-adrenoceptor subtype. (C) 1997 Elsevier Science B.V.