PHARMACOLOGICAL SUBCLASSIFICATION OF ALPHA-1-ADRENOCEPTORS IN VASCULAR SMOOTH-MUSCLE
PHARMACOLOGICAL SUBCLASSIFICATION OF ALPHA-1-ADRENOCEPTORS IN VASCULAR SMOOTH-MUSCLE
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DOI：
10.1111/j.1476-5381.1990.tb14678.x
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发表时间：
1990-01-01
影响因子：
7.3
通讯作者：
OSHITA, M
中科院分区：
文献类型：
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作者：
MURAMATSU, I;OHMURA, T;OSHITA, M
1.我们检验了各种血管中的α 1-肾上腺素受体是否可以通过拮抗剂亲和力或通过对氯乙基可乐定或硝苯地平的敏感性而分为亚型。2去甲肾上腺素和苯肾上腺素均能引起各组织的浓度依赖性收缩，酚妥拉明、育亨宾、哌唑嗪、WB 4101和HV 723均能竞争性抑制去甲肾上腺素和苯肾上腺素的收缩。然而，除了酚妥拉明之外，所有拮抗剂的pA 2值在组织之间存在很大差异。3根据血管亲和力的变化，可将其分为Ⅰ、Ⅱ、Ⅲ三类。在组I（犬肠系膜动脉和静脉，隐静脉）中，HV 723的pA 2值大于9，HV 723和WB 4101的pA 2值比哌唑嗪高约1个对数单位。在第II组（犬颈动脉和大鼠胸主动脉）中，这种亲和力的等级顺序颠倒，其中哌唑嗪比HV 723或WB 4101更有效（pA 2值大于9.5）。另一方面，在第III组（兔肠系膜动脉、胸主动脉和颈动脉以及豚鼠胸主动脉）中，哌唑嗪、HV 723和WB 4101以相似的亲和力抑制去甲肾上腺素反应（pA 2值范围为8 - 9）。4育亨宾抑制去甲肾上腺素和苯丙氨酸的反应，其亲和力低于哌唑嗪、HV 723或WB 4101。组I和组II中育亨宾的pA 2值相似（值大于6.5），大于组III中的pA 2值（值小于6.4）。5.第II组中的α 1-肾上腺素受体选择性地受到乙基可乐定的影响，导致狗颈动脉中去甲肾上腺素反应的不可逆衰减和大鼠胸主动脉中的持续收缩。6硝苯地平对所有血管中α 1-肾上腺素受体介导的收缩没有作用或产生轻微的抑制作用;这些作用与上述组无关。7这些结果表明，血管的α 1-肾上腺素能受体可根据拮抗剂亲和力和它们对氯乙基可乐定而不是硝苯地平的敏感性分为三种亚型（称为α 1H、α 1 L和α 1 N）：表3中总结了每种亚型的特征。亚型α 1H、α 1 L和α 1 N可能分别主要参与组II、III和I中血管对去甲肾上腺素或苯肾上腺素的收缩反应。
1 We examined whether .alpha.1-adrenoceptors in various blood vessels can be divided into subtypes by antagonist affinity or by susceptibility to chloroethylclonidine or nifedipine. 2 Noradrenaline or phenylephrine produced concentration-dependent contractions in all the tissues tested, which were competitively inhibited by phentolamine, yohimbine, prazosin, WB4101 and HV723. However, there were large differences between the tissues in the pA2 values for all the antagonists except phentolamine. 3 The blood vessels could be classified into three groups (I, II and III) on the basis of their affinity variation. In group I (dog mesenteric artery and vein, saphenous vein), the pA2 values for HV723 were greater than 9, and those of HV723 and WB4101 were approximately 1 log unit higher than for prazosin. This rank order of affinity reversed in group II (dog carotid artery and rat thoracic aorta), where prazosin was more potent (pA2 values greater than 9.5) than HV723 or WB4101. In group III (rabbit mesenteric artery, thoracic aorta and carotid artery and guinea-pig thoracic aorta), on the other hand, prazosin, HV723 and WB4101 inhibited the noradrenaline response with a similar affinity (pA2 values ranging from 8 to 9). 4 Yohimbine inhibited the responses to noradrenaline and phenylphrine with a lower affinity than prazosin, HV723 or WB4101. The pA2 values for yohimbine were similar in groups I and II (the values greater than 6.5), which were greater than those in group III (values less than 6.4). 5. The .alpha.1-adrenoceptors in group II were selectively affected by chlorethylclonidine, resulting in an irreversible attenuation of noradrenaline responses in the dog carotid artery and a persistent contraction in the rat thoracic arota. 6 Nifedipine either produced no effect or a slight inhibition of .alpha.1-adrenoceptor-mediated contractions in all the blood vessels; these effects were not correlated to the above groups. 7 These results suggest that .alpha.1-adrenoceptors of blood vessels can be divided into three subtypes (designated as .alpha.1H, .alpha.1L and .alpha.1N) by antagonist affinity and their susceptibility to chloroethylclonidine but not to nifedipine: the characteristics of each subtype are summarized in Table 3. Subtypes .alpha.1H, .alpha.1L and .alpha.1N may be predominantly involved in the contractile responses to noradrenaline or phenylephrine of the blood vessels in groups II, III and I, respectively.