Evidence for a functional α1A‐ (α1C‐) adrenoceptor mediating contraction of the rat epididymal vas deferens and an α1B‐adrenoceptor mediating contraction of the rat spleen
Evidence for a functional α1A‐ (α1C‐) adrenoceptor mediating contraction of the rat epididymal vas deferens and an α1B‐adrenoceptor mediating contraction of the rat spleen
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功能性 α1A-（α1C-）肾上腺素受体介导大鼠附睾输精管收缩和 α1B-肾上腺素受体介导大鼠脾收缩的证据
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
I. Marshall
中科院分区：
文献类型：
--
作者：
R. P. Burt;C. Chapple;I. Marshall
1用具有不同克隆受体亚型选择性的α1受体拮抗剂，研究了α1受体亚型对大鼠附精管和大鼠脾收缩的调节作用。2神经元和神经元外摄取阻断剂可卡因和β-雌二醇使大鼠输精管去甲肾上腺素和去甲肾上腺素的作用增强，但不改变甲氧胺的作用。在有或没有摄取阻滞剂的情况下，激动剂的效力顺序是去甲肾上腺素和甲氧胺。在大鼠脾中，这些激动剂的效力不受可卡因和β-雌二醇的影响，它们的效力顺序与输精管相同。3非亚型选择性α1肾上腺素受体拮抗剂哌唑嗪(1×10−7M)对去甲肾上腺素的收缩有竞争性拮抗作用(PA2 9.2)，但对脾的拮抗作用不明显。然而，脾对苯肾上腺素的收缩可被哌唑嗪(高达1×10−7M)竞争性拮抗，其PA2值为9.2。这表明大鼠脾对去甲肾上腺素有α-1和非α-1肾上腺素受体反应。4氯乙基可乐定(10−4M，30min)对输精管去甲肾上腺素的收缩无明显影响，但使脾去甲肾上腺素和去甲肾上腺素的收缩分别右移30倍和30 0倍。这表明，只有脾的收缩是由α1B-肾上腺素能受体介导的。5WB4101(PA2 9.6)、5-甲基乌拉地尔(PA2 8.7)、酚妥拉明(PA2 8.3)、苯扎西辛(PA2 9.4)、螺环酮(PA2 7.5)、吲哚胺(PA2 8.4)和Bmy7378(PA2 6.7)可竞争性拮抗输精管去甲肾上腺素收缩，这与这些拮抗剂在组织α1A-肾上腺素受体结合研究中的亲和力一致。这些值与表达的α1c受体克隆的亲和力最好，与表达的α1b或α1d受体克隆的亲和力较差。因此，经典的α1a-肾上腺素受体似乎与表达的α1c-肾上腺素能受体克隆相同。6 WB4101(PA28.1)、5-甲基-乌拉地尔(PA27.1)、酚妥拉明(PA273)、苯扎西坦(PA274)、螺环酮(PA279)、吲哚青胺(PA275)和Bmy7378(PA274)均能竞争性拮抗小鼠脾内去氧肾上腺素的收缩，这与这些拮抗剂在组织α1B受体结合研究中的亲和力是一致的。PA2值与这些化合物在表达的α1b受体克隆上的亲和力最好，与表达的α1d或α1c受体克隆的亲和力较差。因此，α1B-肾上腺素受体似乎与表达的α1B-肾上腺素能受体克隆相同。7这些结果为大鼠输精管附睾部介导去甲肾上腺素收缩的α1肾上腺素受体为α1A(α1C)亚型提供了药理学证据，并证实了大鼠脾对苯肾上腺素的收缩是由α1B亚型介导的。
1 The α1‐adrenoceptor subtype mediating contraction of the rat epididymal vas deferens and rat spleen has been investigated by use of α1‐adrenoceptor antagonists that have shown selectivity between the different cloned receptor subtypes. 2 In the rat epididymal vas deferens the potency of noradrenaline and phenylephrine was increased in the presence of neuronal and extra‐neuronal uptake blockers, cocaine and β‐oestradiol, but these did not alter that of methoxamine. The order of potency of the agonists in the presence or absence of uptake blockade was noradrenaline > phenylephrine > methoxamine. In the rat spleen the potency of these agonists was not altered in the presence of cocaine and β‐oestradiol, and their order of potency was the same as in the vas deferens. 3 The non subtype selective α1‐adrenoceptor antagonist prazosin (up to 1 × 10−7M) was found to antagonize contractions to noradrenaline in the vas deferens competitively (pA2 9.2), but only in a non competitive manner in the spleen. Contractions to phenylephrine in the spleen however were competitively antagonized by prazosin (up to 1 × 10−7 M) with a pA2 of 9.2. This suggests that there is an α1‐ and a non α1‐adrenoceptor response to noradrenaline in the rat spleen. 4 Pretreatment with chlorethylclonidine (10−4 M for 30 min) did not alter the noradrenaline contractions in the vas deferens, but contractions to noradrenaline and phenylephrine in the spleen were shifted 30 and 300 fold to the right of the control curve, respectively. This suggests that only the contractions in the spleen were mediated by α1B‐adrenoceptors. 5 The noradrenaline contractions in the vas deferens were competitively antagonized by WB 4101 (pA2 9.6), 5‐methyl‐urapidil (pA2 8.7), phentolamine (pA2 8.3), benoxathian (pA2 9.4), spiperone (pA2 7.5), indoramin (pA2 8.4) and BMY 7378 (pA2 6.7), consistent with the affinities of these antagonists in binding studies on tissue α1A‐adrenoceptors. These values correlated best with their published affinities on the expressed α1c‐adrenoceptor clone and poorly with those at either the expressed α1b‐ or α1d‐adrenoceptor clones. Therefore the classical α1A‐adrenoceptor appears to be the same as the expressed α1c‐adrenoceptor clone. 6 The phenylephrine contractions in the spleen were competitively antagonized by WB 4101 (pA2 8.1), 5‐methyl‐urapidil (pA2 7.1), phentolamine (pA2 7.3), benoxathian (pA2 7.4), spiperone (pA2 7.9), indoramin (pA2 7.5) and BMY 7378 (pA2 7.4), consistent with the affinities of these antagonists in binding studies on tissue α1B‐adrenoceptors. The pA2 values correlated best with the published affinities of these compounds on the expressed α1b‐adrenoceptor clone and poorly with those at either the expressed α1d‐ or α1c‐adrenoceptor clones. Therefore the α1B‐adrenoceptor appears to be the same as the expressed α1b‐adrenoceptor clone. 7 The results provide pharmacological evidence that the α1‐adrenoceptor mediating noradrenaline contractions in the epididymal portion of the rat vas deferens is the α1A‐(α1C) subtype and that contractions to phenylephrine in the rat spleen are mediated by the α1B‐subtype.
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克隆α1-肾上腺素受体亚型的药理学特征：选择性拮抗剂表明第四种亚型的存在。
影响因子：
5
作者：
Schwinn,DA;Lomasney,JW
通讯作者：
Lomasney,JW
氯乙基可乐定揭示的 α1-肾上腺素能受体的异质性。
影响因子：
3.6
作者：
Han,C;Abel,PW;Minneman,KP
通讯作者：
Minneman,KP
大鼠脑中α1-肾上腺素能受体亚型的表征：[3H]WB4104 和[3H]哌唑嗪结合的重新评估。
影响因子：
3.6
作者：
Morrow,AL;Creese,I
通讯作者：
Creese,I
α1C-肾上腺素能受体：信号转导途径和哺乳动物组织异质性的表征。
影响因子：
3.6
作者：
Schwinn,DA;Page,SO;Middleton,JP;Lorenz,W;Liggett,SB;Yamamoto,K;Lapetina,EG;Caron,MG;Lefkowitz,RJ;Cotecchia,S
通讯作者：
Cotecchia,S
影响因子：
3.6
作者：
C. Forray;J. Bard;J. Wetzel;G. Chiu;E. Shapiro;R. Tang;H. Lepor;P. Hartig;R. Weinshank;T. Branchek
通讯作者：
C. Forray;J. Bard;J. Wetzel;G. Chiu;E. Shapiro;R. Tang;H. Lepor;P. Hartig;R. Weinshank;T. Branchek