Bohmann C, Schaible U, Schollmeyer P, Rump L C
Medizinische Universitätsklinik Freiburg, Innere Medizin IV, Germany.
Eur J Pharmacol. 1994 Dec 27;271(2-3):283-92. doi: 10.1016/0014-2999(94)90785-4.
The aim of the present study was to investigate alpha-adrenoceptor modulation of neurotransmission in kidneys of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) and to classify the prejunctional alpha 2-adrenoceptor subtype involved. Kidneys of SHR (12-14 weeks) and age-matched WKY were isolated and the sympathetic nerves were stimulated electrically. The renal nerve stimulation-induced outflow of endogenous noradrenaline was measured by high-pressure liquid chromatography with electrochemical detection (HPLC-ECD). In the presence of uptake blockade by cocaine and corticosterone, the renal nerve stimulation-induced outflow of endogenous noradrenaline was significantly greater in SHR than in WKY at 1 Hz (688 +/- 42 pg/g vs. 525 +/- 46 pg/g) and 4 Hz (5265 +/- 495 pg/g vs. 3544 +/- 245 pg/g). At a stimulation frequency of 1 Hz the alpha 2-adrenoceptor agonist UK 14304 (0.01-1 microM) potently inhibited the renal nerve stimulation-induced outflow of noradrenaline with a pEC50 of 7.49 (7.32-7.68) and a maximum of 91% in SHR and with a pEC50 of 7.46 (7.30-7.74) and a maximum of 92% in WKY. alpha-Adrenoceptor antagonist affinity estimates (pKB values) against UK 14304 at the prejunctional alpha 2-autoreceptors were determined. The rank order of affinities (phentolamine > rauwolscine > 2-(2,6-dimethoxyphenoxyethyl) aminomethyl-1,4-benzodioxane HCl (WB 4101) > prazosin) was identical in SHR and WKY, and comparison with data from radioligand binding, molecular cloning and functional studies in other tissues and cell lines indicates that prejunctional alpha 2-autoreceptors of SHR and WKY kidneys are of the alpha 2D subtype.
本研究的目的是调查自发性高血压大鼠（SHR）和正常血压的Wistar-Kyoto大鼠（WKY）肾脏中神经传递的α-肾上腺素能受体调节作用，并对所涉及的突触前α2-肾上腺素能受体亚型进行分类。分离出12 - 14周龄的SHR和年龄匹配的WKY的肾脏，并对交感神经进行电刺激。通过高压液相色谱-电化学检测法（HPLC-ECD）测量肾神经刺激诱导的内源性去甲肾上腺素流出量。在存在可卡因和皮质酮引起的摄取阻断的情况下，在1Hz（688±42 pg/g对525±46 pg/g）和4Hz（5265±495 pg/g对3544±245 pg/g）时，SHR中肾神经刺激诱导的内源性去甲肾上腺素流出量显著高于WKY。在1Hz的刺激频率下，α2-肾上腺素能受体激动剂UK 14304（0.01 - 1μM）能有效抑制肾神经刺激诱导的去甲肾上腺素流出，在SHR中的pEC50为7.49（7.32 - 7.68），最大抑制率为91%，在WKY中的pEC50为7.46（7.30 - 7.74），最大抑制率为92%。测定了突触前α2-自身受体对UK 14304的α-肾上腺素能受体拮抗剂亲和力估计值（pKB值）。SHR和WKY中亲和力的排序（酚妥拉明>萝芙辛>2-(2,6-二甲氧基苯氧基乙基)氨基甲基-1,4-苯并二恶烷盐酸盐（WB 4101）>哌唑嗪）相同，并且与来自其他组织和细胞系的放射性配体结合、分子克隆和功能研究的数据比较表明，SHR和WKY肾脏的突触前α2-自身受体属于α2D亚型。
