Low-affinity conditions for agonists increase the binding of the antagonist [3H]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 been used to delineate low-affinity conditions for agonists binding to G-protein-linked receptors. The effects of this mixture on [3H]RX821002 (2-methoxyidazoxan) binding to alpha2-adrenoceptors were evaluated in different tissues. The density of alpha2-adrenoceptors in the presence of the mixture was 11, 78 and 60% higher in human cortex (predominant alpha2A), human caudate (alpha2A + alpha2C) and rat kidney (alpha2A + alpha2B), respectively, than in its absence. In rat kidney, masking of alpha2B-adrenoceptors by ARC239 (2-[2-[4-(o-methoxyphenyl)-piperazin-1-yl]-ethyl]-4,4-dimethyl-1,3 -(2H,4H)-isoquinolindione) (50 nM) or masking of alpha2A-adrenoceptors by BRL44408 (2-[2H-(1-methyl-1,3-dihydroisoindole)methyl]-4,5-dihydroimidaz ole) (100 nM) demonstrated that the increase was in the alpha2B-adrenoceptor but not in the alpha2A-adrenoceptor subtype.
Callado
L F
LF
Department of Pharmacology, University of the Basque Country, Leioa, Biscay, Spain. kfbcahel@lg.ehu.es
Meana
J J
JJ
D000317:Adrenergic alpha-Antagonists / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006801:Humans; D019329:Idazoxan / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D007668:Kidney / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008566:Membranes / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects* / Q000378:metabolism; D014316:Tritium
D000317:Adrenergic alpha-Antagonists; D018341:Receptors, Adrenergic, alpha-2; D014316:Tritium; D006165:Guanylyl Imidodiphosphate; C058525:2-methoxyidazoxan; D019329:Idazoxan