Drugs and receptors. An overview of the current state of knowledge.
Drugs and receptors. An overview of the current state of knowledge.
复制标题
药物和受体。
作者：
T. Kenakin
本文综述了利用离体组织包埋药物和药物受体的理论概念和方法。具体的影响，在体外测量的激动剂的亲和力和相对功效，受体结合到细胞膜的脂质双层中的转导蛋白的想法进行了讨论。激动剂-受体平衡的三元复合物形成的影响对激动剂受体平衡解离常数的测量提出了理论异议。可能的“混杂”的受体相对于G-蛋白，它们可以相互作用，使受体的激动剂的分类怀疑。使用Schild分析的拮抗剂的亲和力和随后的受体分类的测量被认为是在最近的数据显示，估计用这种方法计算是异质的。结果分析检测变构效应进行了讨论。最后，分子生物学对药物和药物受体分类过程的影响被认为是，以及在受体水平上的药物作用的病理过程的影响。
This paper reviews the theoretical concepts and methods utilised with isolated tissues to characterise drugs and drug receptors. Specifically the impact, on the in vitro measurement of agonist affinity and relative efficacy, of the idea that receptors bind to transduction proteins in the lipid bilayer of the cell membrane is discussed. The effects of ternary complex formation of agonist-receptor equilibria raise theoretical objections to the measurement of agonist receptor equilibrium dissociation constants. Possible 'promiscuity' of receptors with respect to the G-proteins with which they can interact makes classification of receptors by agonists suspect. The use of Schild analysis for the measurement of antagonist affinity and subsequent classification of receptors is considered in the light of recent data showing that estimates calculated with this method are heterogeneous. Resultant analysis for the detection of allosteric effects is also discussed. Lastly, the impact of molecular biology on the drug and drug receptor classification process is considered, as well as the effects of pathological processes on drug action at the receptor level.