Differential modulation of α 2-adrenoceptor subtypes in rat kidney by chronic desipramine treatment

Abstract

The profile of [ 3H]RX821002 (2-methoxy idazoxan) binding to α 2-adrenoceptor subtypes in rat kidney membranes was evaluated in controls and after chronic treatment with desipramine (10 mg/kg, i.p., every 12 h, 7 days) or clorgyline (2 mg/kg, i.p., every 24 h, 21 days). [ 3H]RX821002 recognized with high affinity (K d = 1.5 ± 0.2 nM in controls) a single and saturable population of binding sites (B max = 57 ± 5 fmol/mg protein in controls). The competitions by (−)-adrenaline, the α 2B-adrenoceptor selective drug ARC239 (2-[2-[4-(o-methoxyphenyl)-piperazin-1-yl]-ethyl]-4, 4-dimethyl-1,3(2H,4H)-isoquinolindione) and the α 2A-adrenoceptor selective drug BRL44408 (2-[2H-(1-methyl-1,3-dihydroisoindole)methyl]-4,5-dihydroimidazole) suggested the existence of both α 2A- and α 2B-adrenoceptors together with a non-adrenoceptor binding site. After chronic desipramine but not after chronic clorgyline treatments, the density (B max) of α 2-adrenoceptors was increased (46%). In the presence of ARC239 (50 nM), the density of α 2A-adrenoceptors increased (44%) in the desipramine-treated group without changes in the clorgyline-treated group. Conversely, in the presence of BRL44408 (100 nM), the density of α 2B-adrenoceptors was not affected by the treatments. The selective upregulation of the α 2A-adrenoceptor subtype following chronic desipramine administration is compatible with a differential location and function of the α 2-adrenoceptor subtypes in the rat kidney.