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[3H]RX821002 (2-methoxyidazoxan) binds to α2-adrenoceptor subtypes and a non-adrenoceptor imidazoline binding site in rat kidney

1996; Elsevier BV; Volume: 316; Issue: 2-3 Linguagem: Inglês

10.1016/s0014-2999(96)00692-9

1879-0712

Luís F. Callado, Ane M. Gabilondo, J. Javier Meana,

Neuroscience and Neuropharmacology Research

The binding of [3H]RX821002 (2-methoxyidazoxan) was evaluated in rat kidney membranes. [3H]RX821002 (0.13–16 nM) recognized a single, saturable binding site with high affinity. Different binding site densities were calculated depending on non-specific binding as defined by (−)-adrenaline or RX821002 (10 μM). Competition assays using (−)-adrenaline and the subtype-selective drugs ARC 239 (2-[2-[4-(o-methoxyphenyl)-piperazin-l-yl]-ethyl]4,4-dimethyl-1,3(2mH,4H-isoquinolindione), BRL 44408 (2-[2H-(1-methyl-1,3-dihydroisoindole)methyl]-4,5-dihydroimidazole), oxymetazoline or prazosin for [3H]RX821002 binding sites revealed the presence of α2B-adrenoceptors (33–51%), α2D-adrenoceptors (15–28%) and an adrenaline-insensitive population (34–40%), sensitive to imidazolines. After the addition of (−)-adrenaline (3 μM) to mask α2-adrenoceptors, [3H]RX821002 specifically identified a saturable binding site with high affinity (Kd = 4.9 ± 1.5 nM). The pharmacological profile of this non-adrenoceptor, [3H]RX821002 binding site (potencies: efaroxan > clonidine > guanabenz > BRL 44408 > ARC 239 > BU 224 (2-(4,5-dihydroimidaz-2-yl)quinoline) > moxonidine > (−)-noradrenaline > cimetidine) is different to that of imidazoline I1 or imidazoline I2 binding sites. Alternative incubation in the presence of ARC 239 (50 nM) to mask α2B-adrenoceptors or BRL 44408 (100 nm) to mask α2D-adrenoceptors confirmed the existence of both α2-adrenoceptor subtypes and a non-adrenoceptor imidazoline binding site.