Lefkowitz R J, Cotecchia S, Samama P, Costa T
Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710.
Trends Pharmacol Sci. 1993 Aug;14(8):303-7. doi: 10.1016/0165-6147(93)90048-O.
Adrenoceptors are prototypic members of the superfamily of seven transmembrane domain, G protein-coupled receptors. Study of the properties of several mutationally activated adrenoceptors is deepening understanding of the normal functioning of this ubiquitous class of receptors. The new findings suggest an expansion of the classical ternary complex model of receptor action to include an explicit isomerization of the receptors from an inactive to an active state which couples to the G protein ('allosteric ternary complex model'). This isomerization involves conformational changes which may occur spontaneously, or be induced by agonists or appropriate mutations which abrogate the normal 'constraining' function of the receptor, allowing it to 'relax' into the active conformation. Robert Lefkowitz and colleagues discuss the physiological and pathophysiological implications of these new insights into regulation of receptor activity.
肾上腺素能受体是七跨膜结构域G蛋白偶联受体超家族的典型成员。对几种经突变激活的肾上腺素能受体特性的研究正在加深对这类普遍存在的受体正常功能的理解。新发现表明，受体作用的经典三元复合物模型有所扩展，纳入了受体从无活性状态到与G蛋白偶联的活性状态的明确异构化（“变构三元复合物模型”）。这种异构化涉及构象变化，其可能自发发生，或由激动剂或适当突变诱导，这些突变消除了受体正常的“约束”功能，使其能够“松弛”成活性构象。罗伯特·莱夫科维茨及其同事讨论了这些关于受体活性调节的新见解的生理和病理生理意义。
