Are there multiple imidazoline binding sites?
Are there multiple imidazoline binding sites?
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是否有多个咪唑啉结合位点？
DOI：
10.1016/0165-6147(89)90002-3
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发表时间：
1989
影响因子：
13.8
通讯作者：
P. Insel
中科院分区：
文献类型：
--
作者：
M. Michel;P. Insel
咪唑啉（例如可乐定和妥拉唑啉）因其广泛的实验和临床用途而成为一类重要的化合物。某些咪唑啉与uZ-肾上腺素受体具有高特异性和亲和力相互作用，因此已被放射性标记并用作放射性配体来识别和量化这些受体。这些配体的结合位点的α1-肾上腺素能性质通过观察证实，它们对儿茶酚胺和α1-肾上腺素受体选择性拮抗剂如萝芙素具有高亲和力，但对α1-肾上腺素受体选择性拮抗剂如哌唑嗪具有低亲和力。然而，最近的证据表明，具有咪唑啉结构的α-肾上腺素受体放射性配体，例如[3H] p-NHZ-可乐定（[3H]-PAC）或rH]咪唑克生（图1），也可以结合到不被儿茶酚胺竞争的位点，表明这些额外位点不是肾上腺素受体。这些结合位点在生化特性和α方面也不同于CW-肾上腺素受体。解剖位置1* 2：此外，它们似乎不是多巴胺、S-HT 或组胺%'的受体。有些令人惊讶的是，以前被认为对α-肾上腺素能受体具有高特异性的某些药物能够以高亲和力识别这些结合位点。由于大多数这些“高亲和力”药物都具有咪唑啉结构，因此非肾上腺素能 Sir&s 被称为“咪唑啉偏好结合位点”。它们已在兔、大鼠、猪和人类的各种组织（例如肾和脑）以及人红白血病细胞系3-13中得到证实。然而，咪唑啉偏好结合位点的药理学特征根据所研究的物种和所使用的放射性配体的不同而有很大差异。在本文中，我们讨论了咪唑啉偏好的药物特异性和可能的生理相关性。这种类型的结合位点，特别是其明显的异质性。
Imidazolines (eg clonidine and tolazoline) are an important class of compound because of their wide experimental and clinical use.?, ome imidazolines interact with higli specificity and affinity with uZ-adrenoceptors and have therefore been radiolabelled and used as radioligands to identify and quantify these receptors. The a,-adrenergic nature of binding sites for these ligands was confirmed by the observation that they have high affinity for catecholamines and a,-adrenoceptorselective antagonists such as rauwolscine, but low affinity for a,-adrenoceptor-selective antagonists such as prazosin. Recent evidence, however, shows that a-adrenoceptor radioligands with an imidazoline structure-[3H] p-NHz-clonidine ([3H]-PAC) or rH] idazoxan, for example (Fig. 1)-can also bind to sites that are not competed for by catecholamines, suggesting that these additional sites are not adrenoceptors. These binding sites also differ from cw-adrenoceptors in their biochemical properties and in their a. tatomical location1* 2: Moreover, they dc not appear to be receptors for dopamine, S-HT or histamine%‘. Somewhat surprisingly, certain drugs that were previously considered to have high specificity for ar-adrenoceptors recognize these binding sites with high affinity. As most of these ‘high affinity’drugs have an imidazoline structure, the non-adrenergic sir&s have been termed ‘imidazoline-preferring binding sites’. They have been demonstrated in various tissues (eg kidney and brain) of rabbits, rats, pigs and humans, as well as in the human erythroleukemia cell line3-13. However, the pharmacological characteristics of the imidazoline-preferring binding sites differ considerably depending on the species investigated and the radioligand used. In this article we discuss the pha~ acologic~ specificity and possible physiological relevance of imidazoline-preferring. binding sites of this type, with special regard to their apparent heterogeneiti.
α-2 肾上腺素受体异质性的解剖学证据：大鼠脑中 [3H]rauwolscine 和 [3H]idazoxan 的放射自显影差异分布。
DOI：
--
发表时间：
1987
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Boyajian,CL;Loughlin,SE;Leslie,FM
通讯作者：
Leslie,FM
[3H]咪唑克生和一些其他α2-肾上腺素能药物也以高亲和力结合至非肾上腺素能位点。
影响因子：
3.6
作者：
Michel,MC;Brodde,OE;Schnepel,B;Behrendt,J;Tschada,R;Motulsky,HJ;Insel,PA
通讯作者：
Insel,PA