The receptor concept in evolution
The receptor concept in evolution
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进化中的受体概念
DOI：
10.1016/0006-2952(77)90465-8
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发表时间：
1977
影响因子：
5.8
通讯作者：
A. J. Beld
中科院分区：
文献类型：
--
作者：
E. J. Ariëns;A. J. Beld
对药物作用的正确理解需要分子方法，因为生物活性剂只能通过其分子与生物对象中的某些对应物之间的相互作用而在生物对象中诱导药理作用。因此，药物的化学性质是其作用和活性的决定因素，化学性质和作用之间必须存在关系[1]。基于尼古丁的实验，兰利[2]在50多年前已经引入了存在于生物对象中的受体物质的概念，药物必须与该受体物质相互作用以发挥其生物效应。从那时起，受体的概念，特别是药物-受体相互作用作为药物作用基础的观点已经发展。从一个纯粹的概念性受体的想法开始，它的完全实现现在已经实现了在几个实验室中的烟碱乙酰胆碱受体的分离[3 - 13]。基于与放射性标记配体的直接结合研究，已经确定了β 1-肾上腺素能受体[14~17]、毒蕈碱乙酰胆碱受体[18 26]、胰岛素受体[27 29]、雌激素受体[30 - 33]和许多其他未单独提及的受体的存在（参见综述文章[81 83]）。药物的分子作用部位，即活性剂必须与之相互作用以诱导所考虑的效应的那些分子，被称为特异性受体。它们位于靶细胞内或靶细胞上，而靶细胞不一定是产生效应的细胞。被认为是效应的参数在一定程度上是任意的。例如，惊厥剂士的宁的受体位于中枢神经系统，但惊厥是在横纹肌中产生的。事实上，脑电图的变化也可以作为效应而不是惊厥来测量。药物作用的基础过程可以分为三个主要阶段：药物阶段，包括活性药物从其剂型中释放的过程，从而确定可供吸收的浓度（药物可得性）;药代动力学阶段包括在药物的吸收、分布、代谢转化和排泄中起作用的过程，测定血浆中活性剂的浓度，从而测定作用部位的活性剂浓度（生物利用度）;药效学阶段包括活性剂与其分子作用位点之间的相互作用，引发刺激，通过涵盖刺激的转导、放大和调节的一系列过程导致
A proper understanding of drug action requires a molecular approach, since a bioactive agent can only induce a pharmacological effect in a biological object as the result of an interaction between its molecules and certain counterparts in the biological object. Consequently the chemical properties of a drug are determinant for its action and activity, and a relationship between chemical properties and action must exist [1]. Based on experiments with nicotine Langley [2] introduced more than 50 years ago already the concept of a receptor substance present in the biological object with which a drug has to interact in order to exert its biological effect. Since then the receptor concept and especially the views on drug-receptor interaction as a basis for drug action have evolved. Starting from a purely conceptual receptor idea its full materialization has been realized now with the isolation of the nicotinic acetylcholine receptor in several laboratories [3-13]. The existence of fl-adrenergic receptors [14~ 17], muscarinic acetylcholine receptors [18 26], insulin receptors [27 29], estrogen receptors [30-33] and many others not to be mentioned separately have been firmly established on basis of direct binding studies with radioactively labeled ligands (see review articles [81 83]). The molecular sites of action of drugs, ie those molecules with which the active agent must interact in order to induce the effect considered, are called the specific receptors. They are located in or on target cells, which are not necessarily the cells in which the effect is generated. The parameter, considered as effect, is to a certain degree arbitrary. The receptors for the convulsant agent strychnine, for instance, are located in the central nervous system, but the convulsions are generated in the striated muscle. Instead of the convulsions, as a matter of fact also the changes in the electroencephalogram may be measured as the effect.The sequence of processes at the basis of drug action can be divided into three main phases: the pharmaceutical phase comprising the release processes of the active drug from its dosage form, thus determining the concentration available for absorption (the pharmaceutical availability); the pharmacokinetic phase comprising the processes that play a part in the absorption, distribution, metabolic conversion and excretion of the drug, determining the concentration of the active agent in the plasma and thus at the site of action (the biological availability); the pharmacodynamic phase comprising the interaction between the active agent and its molecular sites of action, initiating a stimulus, leading via a sequence of processes covering the transduction, amplification and modulation of the stimulus to the change in the