Argyle S A, McGrath J C
Autonomic Physiology Unit, Division of Neuroscience and Biomedical Systems, Institute of Biomedical & Life Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom.
J Pharmacol Exp Ther. 2000 Nov;295(2):627-33.
To determine the characteristics of the alpha(1)-adrenoceptor subtypes involved in adrenergic regulation of peripheral vascular resistance, contraction of canine subcutaneous resistance arteries was studied using wire myographs. The potencies of agonists and antagonists, chosen for their ability to discriminate between alpha(1)-adrenoceptor subtypes, were assessed in the presence of cocaine (3 microM), corticosterone (30 microM), and propranolol (1 microM). The rank order of agonist potency (pEC(50) +/- S.E.) was (R)-A-61603 (7.88 +/- 0.1) > norepinephrine (6.41 +/- 0.1) > phenylephrine (5.83 +/- 0.1). The high sensitivity to (R)-A-61603 relative to phenylephrine is inconsistent with the presence of the alpha(1D)-adrenoceptor and most consistent with an alpha(1A)-adrenoceptor response. This is supported by the low affinity for the alpha(1D)-selective antagonist BMY 7378 (pK(B) 6.51 +/- 0.47). The low pA(2) values for prazosin (8.36) and HV723 (8.81), by definition, indicate the involvement of the putative alpha(1L)-adrenoceptor, a hypothesis supported by the pA(2) values for WB4101 (8.42) and 5-methyl-urapidil (8.08). Pre-exposure to 1 microM CEC had little effect, whereas 100 microM CEC reduced the maximum contraction but not the sensitivity to norepinephrine. This low sensitivity to CEC argues against the presence of the alpha(1B)-adrenoceptor. We conclude that, by current definitions, an alpha(1A)-/alpha(1L)-adrenoceptor causes contraction of these vessels. This does not support the concept that selectivity for the alpha(1A)-adrenoceptor is the basis for the effectiveness of some alpha-blockers in some tissues, such as prostate, but not in other tissues such as blood vessels. Rather, the generally low potency of alpha-blockers in some tissues may be due to a tissue-specific property of the receptors.
为了确定参与肾上腺素能调节外周血管阻力的α(1)-肾上腺素能受体亚型的特征，我们使用线肌张力测定仪研究了犬皮下阻力动脉的收缩情况。选用了能够区分α(1)-肾上腺素能受体亚型的激动剂和拮抗剂，在存在可卡因（3微摩尔）、皮质酮（30微摩尔）和普萘洛尔（1微摩尔）的情况下评估其效力。激动剂效力的排序（pEC(50)±标准误）为：(R)-A-61603（7.88±0.1）>去甲肾上腺素（6.41±0.1）>去氧肾上腺素（5.83±0.1）。相对于去氧肾上腺素，对(R)-A-61603的高敏感性与α(1D)-肾上腺素能受体的存在不一致，而与α(1A)-肾上腺素能受体反应最为一致。这得到了对α(1D)-选择性拮抗剂BMY 7378的低亲和力（pK(B) 6.51±0.47）的支持。哌唑嗪（8.36）和HV723（8.81）的低pA(2)值，根据定义，表明假定的α(1L)-肾上腺素能受体参与其中，这一假设得到了WB4101（8.42）和5-甲基-乌拉地尔（给你补充完整：5-甲基-乌拉地尔（8.08））的pA(2)值的支持。预先暴露于1微摩尔CEC几乎没有影响，而100微摩尔CEC降低了最大收缩，但没有降低对去甲肾上腺素的敏感性。对CEC的这种低敏感性表明不存在α(1B)-肾上腺素能受体。我们得出结论，根据目前的定义，α(1A)-/α(1L)-肾上腺素能受体导致这些血管收缩。这并不支持这样的概念：对α(1A)-肾上腺素能受体的选择性是某些α-阻滞剂在某些组织（如前列腺）而非其他组织（如血管）中有效的基础。相反，α-阻滞剂在某些组织中的效力普遍较低可能是由于受体的组织特异性特性。
补充完整后的翻译更符合完整的英文原文意思，你可以根据实际需求进行调整。如果你还有其他疑问，欢迎继续向我提问。
