Molecular characterization of adrenergic receptors.
Molecular characterization of adrenergic receptors.
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肾上腺素能受体的分子表征。
DOI：
10.1161/01.res.56.5.635
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发表时间：
1985
影响因子：
20.1
通讯作者：
Graham,RM
中科院分区：
文献类型：
--
作者：
Homcy,CJ;Graham,RM
这是一个适当的时间来审查在肾上腺素能受体领域的进展，特别是在研究方面，旨在实现对这些蛋白质的分子组成水平的理解。在过去的十年中，肾上腺素能受体药理学领域出现了爆炸式的发展，这在很大程度上是由于放射性配体结合试验的发展。在各种生理条件下发生的受体数量和亲和力的变化现已被记录。可以给出许多例子，例如甲状腺机能亢进症中受体数量的增加（威廉姆斯等人，一九七七年; Tsai和Chen，1978）、甲状腺功能减退症中受体数量减少（Ciaraldi和Marinetti，1975; Banerjee和Kung，1977）或在甲状腺激素异常（Stiles和Lefkowitz，1981）或类固醇激素水平异常（Davies等人，1981年）。然而，这类研究往往不能清楚地界定所观察到的现象背后的机制。在最简单的情况下，受体测定可以精确地确定所观察到的生理反应的改变是否发生在受体水平或其远端。在少数情况下，明确的结果表明，对肾上腺素能激动剂的反应性改变不在受体水平。例如，与成年犬相比，尽管受体数量更多、亲和力不变和环化酶活化增强，但新生犬对肾上腺素能激动剂的显著低反应性是明显的（Rockson et al.，1981年）。不太常见的是，可以深入了解潜在的机制。最好的例子之一是受体脱敏的过程，其中生理反应在连续暴露于激动剂时减弱（Harden，1983）。不仅由于在某些系统中这些受体的明显内化而记录了受体从细胞表面的损失，而且在某些模型中观察到受体与其效应系统腺苷酸环化酶的实际解偶联作为早期事件。应用放射性配体结合分析这个问题表明，脱敏可能受到不同的机制，这取决于物种和组织类型检查，甚至通过组合的机制。然而，很明显，对各种组分如何产生跨膜信息、调节或减弱这种激活的因素以及相互作用组分的化学计量的明确理解将仅来自于它们的纯化和重组到人工膜系统中。α-肾上腺素能受体α-肾上腺素能受体是整合的膜蛋白，与其他膜结合受体一样，可能跨越脂质双层。与0-肾上腺素能受体非常相似，这些受体蛋白在与内源性儿茶酚胺、去甲肾上腺素和肾上腺素相互作用后介导交感神经系统的作用（Mayer，1980; Graham，1981）。α-和β-肾上腺素能受体以相当的亲和力结合内源性儿茶酚。然而，通过它们在不同组织中介导的相反效应以及它们对合成配体的亲和力（其可以相差多达一百万倍），它们容易地被区分（Graham，1981）。此外，尽管a-和/？-肾上腺素能受体具有许多相似的生物物理和生物化学性质，如下文所详述的，现在有充分的证据表明它们是不同的蛋白质。
THIS is an appropriate time to review progress in the area of adrenergic receptors, particularly in terms of research that aims at achieving an understanding of these proteins at the level of their molecular composition. The past decade has seen an explosion in the field of adrenergic receptor pharmacology, made possible to a large extent by the development of the radioligand-binding assay. Alterations in receptor number and affinity occurring under a variety of physiological conditions have now been documented. Numerous examples can be given, such as an increase in receptor number in hyperthyroidism (Williams et al., 1977; Tsai and Chen, 1978), decreased receptor number in hypothyroidism (Ciaraldi and Marinetti, 1975; Banerjee and Kung, 1977) or alterations in receptor-effector coupling seen in cases of abnormal thyroid hormone (Stiles and Lefkowitz, 1981) or steroid hormone levels (Davies et al., 1981). It is not often, however, that such studies can clearly define the mechanisms underlying the observed phenomena. In the simplest case, the receptor assay may pinpoint whether an observed alteration in the physiological response occurs at the receptor level or distal to it. In a few cases, unambiguous results indicate that the altered responsiveness to an adrenergic agonist is not at the receptor level. For example, a marked hyporesponsiveness to adrenergic agonists is apparent in the neonatal dog, despite the greater numbers of receptors, an unaltered affinity, and enhanced cyclase activation, as compared to the adult (Rockson et al., 1981). Less commonly, insights into underlying mechanisms can be gained. One of the best examples is the process of receptor desensitization, whereby the physiological response becomes attenuated on continuous exposure to an agonist (Harden, 1983). Not only has a loss of receptors from the cell surface been documented due to an apparent internalization of these receptors in some systems, but also an actual uncoupling of the receptor from its effector system, adenylate cyclase, has been observed as an early event in certain models. Application of the radioligandbinding assay to this problem has indicated that desensitization may be effected by different mechanisms, depending on the species and tissue type examined, or even through a combination of mechanisms. However, it is clear that a definitive understanding of how various components produce a transmembrane message, of the factors modulating or attenuating this activation, and of the stoichiometry of the interactive components will come only from their purification and reconstitution into artificial membrane systems. a-Adrenergic Receptors a-Adrenergic receptors are integral membrane proteins that, like other membrane-bound receptors, probably span the lipid bilayer. Much like 0-adrenergic receptors, these receptor proteins mediate the actions of the sympathetic nervous system following interaction with endogenous catecholamines, norepinephrine and epinephrine (Mayer, 1980; Graham, 1981). Both a-and (3-adrenergic receptors bind the endogenous catechols with comparable affinity. However, they are readily distinguished by their differing effector-coupled responses, by the opposing effects that they mediate in different tissues, and by their affinities for synthetic ligands, which can differ by as much as one million-fold (Graham, 1981). Further, whereas a-and/?-adrenergic receptors have a number of similar biophysical and biochemical properties, as will be detailed below, there is now ample evidence to indicate that they are distinct proteins.
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纯β-肾上腺素能受体：单一多肽赋予儿茶酚胺对腺苷酸环化酶的反应性
影响因子：
64.8
作者：
R. Cerione;B. Strulovici;J. Benovic;R. Lefkowitz;M. Caron
通讯作者：
M. Caron
Na对人血小板α2-肾上腺素能受体系统的影响。
DOI：
--
发表时间：
1983
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Connolly,TM;Limbird,LE
通讯作者：
Limbird,LE
α-肾上腺素能受体分类的功能基础
DOI：
--
发表时间：
1977
期刊：
影响因子：
--
作者：
S. Berthelsen;W. Pettinger
通讯作者：
W. Pettinger
从cDNA序列推导出加州鱼雷乙酰胆碱受体α亚基前体的一级结构
影响因子：
64.8
作者：
M. Noda;Hideo Takahashi;T. Tanabe;M. Toyosato;Y. Furutani;T. Hirose;M. Asai;S. Inayama;T. Miyata;S. Numa
通讯作者：
S. Numa
腺苷酸环化酶的抑制性鸟嘌呤核苷酸结合调节成分。
DOI：
--
发表时间：
1984
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Katada,T;Bokoch,GM;Northup,JK;Ui,M;Gilman,AG
通讯作者：
Gilman,AG