Feng F, Pettinger W A, Abel P W, Jeffries W B
Midwest Hypertension Research Institute, Omaha, Nebraska.
J Pharmacol Exp Ther. 1991 Jul 1;258(1):263-8.
alpha 1-Adrenoceptors are expressed in high density in the rat kidney. Recent studies have shown that alpha 1-adrenoceptors are heterogeneous and can be subtyped based on their affinity for the antagonists WB 4101 (alpha 1A greater than alpha 1B) and chloroethylclonidine (alpha 1B-selective). We therefore investigated the distribution of alpha 1-adrenoceptor subtypes using [3H]prazosin binding in membranes prepared from cortex, the outer stripe of the outer medulla (OSOM), the inner stripe of the outer medulla (ISOM) and inner medulla dissected from rat kidney. [3H]Prazosin binding was detectable in each region with the following maximum binding site values for [3H]prazosin (femtomoles per milligram of protein): cortex, 186 +/- 20; OSOM, 76 +/- 14; ISOM, 34 +/- 2; and inner medulla, 8 +/- 2. Pretreatment of membranes with chloroethylclonidine (10 microM for 10 min) reduced maximum binding sites to 41 +/- 4% (75 +/- 9 fmol/mg) of control in cortex, 41 +/- 9% of control in OSOM (29 +/- 8 fmol/mg) and 15 +/- 3% of control in ISOM (5 +/- 1 fmol/mg). In competition studies, WB 4101 labeled both high and low affinity sites in cortex (respective pKi values = 10.01 +/- 0.3 and 8.23 +/- 0.1) and OSOM (pKi values = 9.6 + 0.3 and 8.3 +/- 0.5), but only low affinity sites in ISOM (pKi = 8.41 +/- 0.1). The relative prevalence of high:low affinity sites revealed by WB 4101 was 53:47 for cortex, 52:48 for OSOM and virtually all low affinity for ISOM. Prior treatment with chloroethylclonidine greatly reduced the low affinity component of the WB 4101 competition curve in cortex and OSOM. We conclude that: 1) the density of alpha 1-adrenoceptors is highest in the cortex and decreases from cortex to papilla and 2) the alpha 1A and alpha 1B subtypes are approximately equally distributed in the cortex and OSOM, but the alpha 1B subtype predominates in ISOM.
α1-肾上腺素能受体在大鼠肾脏中高表达。最近的研究表明，α1-肾上腺素能受体具有异质性，可根据其对拮抗剂WB 4101（α1A大于α1B）和氯乙可乐定（α1B选择性）的亲和力进行亚型分类。因此，我们使用[3H]哌唑嗪结合法，研究了从大鼠肾脏分离的皮质、外髓质外层条纹（OSOM）、外髓质内层条纹（ISOM）和内髓质制备的膜中α1-肾上腺素能受体亚型的分布。在每个区域都可检测到[3H]哌唑嗪结合，[3H]哌唑嗪的最大结合位点值如下（每毫克蛋白质的飞摩尔数）：皮质，186±20；OSOM，76±14；ISOM，34±2；内髓质，8±2。用氯乙可乐定（10μM，10分钟）预处理膜后，皮质中最大结合位点降至对照的41±4%（75±9 fmol/mg），OSOM中降至对照的41±9%（29±8 fmol/mg），ISOM中降至对照的15±3%（5±1 fmol/mg）。在竞争研究中，WB 4101在皮质（各自的pKi值=10.01±0.3和8.23±0.1）和OSOM（pKi值=9.6±0.3和8.3±0.5）中标记了高亲和力和低亲和力位点，但在ISOM中仅标记了低亲和力位点（pKi=8.41±0.1）。WB 4101显示的高亲和力：低亲和力位点的相对比例在皮质中为53:47，在OSOM中为52:48，而在ISOM中几乎全是低亲和力位点。预先用氯乙可乐定处理可大大降低皮质和OSOM中WB 4101竞争曲线的低亲和力成分。我们得出结论：1）α1-肾上腺素能受体密度在皮质中最高，从皮质到乳头逐渐降低；2）α1A和α1B亚型在皮质和OSOM中分布大致相等，但α1B亚型在ISOM中占主导。
