Differential modulation of alpha2-adrenoceptor subtypes in rat kidney by chronic desipramine treatment.
The profile of [3H]RX821002 (2-methoxy idazoxan) binding to alpha2-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 (Kd=1.5+/-0.2 nM in controls) a single and saturable population of binding sites (Bmax=57+/-5 fmol/mg protein in controls). The competitions by (-)-adrenaline, the alpha2B-adrenoceptor selective drug ARC239 (2-[2-[4-(o-methoxyphenyl)-piperazin-1-yl]-ethyl]-4,4-dimethyl-1,3 (2H,4H)-isoquinolindione) and the alpha2A-adrenoceptor selective drug BRL44408 (2-[2H-(1-methyl-1,3-dihydroisoindole)methyl]-4,5-dihydroimidaz ole) suggested the existence of both alpha2A- and alpha2B-adrenoceptors together with a non-adrenoceptor binding site. After chronic desipramine but not after chronic clorgyline treatments, the density (Bmax) of alpha2-adrenoceptors was increased (46%). In the presence of ARC239 (50 nM), the density of alpha2A-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 alpha2B-adrenoceptors was not affected by the treatments. The selective upregulation of the alpha2A-adrenoceptor subtype following chronic desipramine administration is compatible with a differential location and function of the alpha2-adrenoceptor subtypes in the rat kidney.
Callado
L F
LF
Department of Pharmacology, University of the Basque Country, Bizkaia, Spain. L.F.Callado@mds.qmw.ac.uk
Gabilondo
A M
AM
Meana
J J
JJ
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D003010:Clorgyline / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology*; D004837:Epinephrine / Q000378:metabolism; D019329:Idazoxan / Q000031:analogs & derivatives / Q000378:metabolism; D007093:Imidazoles / Q000378:metabolism; D066298:In Vitro Techniques; D007211:Indoles / Q000378:metabolism; D054833:Isoindoles; D007546:Isoquinolines / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D010879:Piperazines / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000145:classification / Q000187:drug effects* / Q000378:metabolism*
D018759:Adrenergic Uptake Inhibitors; D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D007211:Indoles; D054833:Isoindoles; D007546:Isoquinolines; D008996:Monoamine Oxidase Inhibitors; D010879:Piperazines; D018341:Receptors, Adrenergic, alpha-2; C058525:2-methoxyidazoxan; D003010:Clorgyline; C032994:AR-C239; D003891:Desipramine; D019329:Idazoxan; D004837:Epinephrine; C072125:BRL 44408