Trendelenburg A U, Limberger N, Rump L C
Pharmakologisches Institut, Universitätsklinikum, Freiburg, Germany.
Mol Pharmacol. 1994 Jun;45(6):1168-76.
The pharmacological properties of the alpha 2-adrenergic receptors regulating the release of norepinephrine were investigated in human kidney cortex. Slices were preincubated with [3H]norepinephrine, superfused in the presence of desipramine, and stimulated electrically. Two procedures were used to estimate the affinity of alpha-adrenergic antagonists at the autoreceptors. First, pEC30 values (negative logarithms of antagonist concentrations that increased the electrically evoked overflow of tritium by 30%) were determined. Second, antagonist pKd values were determined against the overflow-inhibiting effect of the alpha 2 receptor-selective agonist UK 14,304. Antagonist pEC30 values correlated well with the respective pKd values (r = 0.96, p < 0.01). The site of action of the phenylethylamine norepinephrine, as well as of the imidazoline derivative UK 14,304, is an alpha 2-adrenergic receptor. Neither the cyclooxygenase inhibitor indomethacin nor the adenosine receptor antagonist 8-sulfophenyltheophylline changed the concentration-inhibition curve of UK 14,304. When compared with binding data from the literature, the pEC30 values correlated best with the antagonist affinities at alpha 2c binding sites in an opossum kidney cell line and rat brain cortex (r > or = 0.95, p < 0.001) and at the affinities of alpha 2c sites obtained in COS cells transfected with either the human alpha 2-C4 or rat RG10-alpha 2 gene (r > or = 0.95, p < 0.01). In contrast, the correlations with alpha 2A, alpha 2B, and alpha 2D sites were not as good. Moreover, the alpha 2-autoreceptors in human kidney cortex were very similar to the alpha 2C-adrenergic receptors mediating prostaglandin synthesis in rabbit aorta but differed from alpha 2A- and alpha 2D-autoreceptors in rabbit and rat tissues. It is concluded that in human kidney cortex prejunctional autoreceptors are alpha 2C.
在人肾皮质中研究了调节去甲肾上腺素释放的α2 - 肾上腺素能受体的药理学特性。切片先用[3H]去甲肾上腺素预孵育，在存在地昔帕明的情况下进行灌流，并进行电刺激。采用两种方法来估计α - 肾上腺素能拮抗剂对自身受体的亲和力。首先，测定pEC30值（使氚的电诱发溢出增加30%的拮抗剂浓度的负对数）。其次，针对α2受体选择性激动剂UK 14,304的溢出抑制作用测定拮抗剂的pKd值。拮抗剂的pEC30值与各自的pKd值相关性良好（r = 0.96，p < 0.01）。苯乙胺去甲肾上腺素以及咪唑啉衍生物UK 14,304的作用位点是α2 - 肾上腺素能受体。环氧化酶抑制剂吲哚美辛和腺苷受体拮抗剂8 - 磺苯基茶碱均未改变UK 14,304的浓度 - 抑制曲线。与文献中的结合数据相比，pEC30值与负鼠肾细胞系和大鼠脑皮质中α2c结合位点的拮抗剂亲和力相关性最佳（r≥0.95，p < 0.001），并且与用人类α2 - C4或大鼠RG10 - α2基因转染的COS细胞中获得的α2c位点的亲和力相关性最佳（r≥0.95，p < 0.01）。相比之下，与α2A、α2B和α2D位点的相关性则没那么好。此外，人肾皮质中的α2自身受体与介导兔主动脉中前列腺素合成的α2C - 肾上腺素能受体非常相似，但与兔和大鼠组织中的α2A - 和α2D - 自身受体不同。结论是人肾皮质中的节前自身受体为α2C。
