{"title":"激动作用和偏倚信号。","authors":"Terry Kenakin","doi":"10.1007/164_2025_770","DOIUrl":null,"url":null,"abstract":"<p><p>This chapter considers biased signaling as a natural function of G protein-coupled receptors (GPCRs) in the form of probe dependence. Thus, any ligand that changes the conformation of the receptor (agonist, antagonist, or allosteric modulator) has the potential to change the natural signaling of the receptor through unequal conformational alterations in the receptor structure. This gives an added dimension to agonist selectivity beyond extracellular recognition, namely the ability of agonists to emphasize certain signaling pathways in the cell at the expense of others. Given this, selectivity is discussed in terms of varying intrinsic efficacy and selective stabilization of receptor states with methods to detect and measure these effects. Last, the translation of in vitro to complex in vivo systems will be considered.</p>","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Agonism and Biased Signaling.\",\"authors\":\"Terry Kenakin\",\"doi\":\"10.1007/164_2025_770\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>This chapter considers biased signaling as a natural function of G protein-coupled receptors (GPCRs) in the form of probe dependence. Thus, any ligand that changes the conformation of the receptor (agonist, antagonist, or allosteric modulator) has the potential to change the natural signaling of the receptor through unequal conformational alterations in the receptor structure. This gives an added dimension to agonist selectivity beyond extracellular recognition, namely the ability of agonists to emphasize certain signaling pathways in the cell at the expense of others. Given this, selectivity is discussed in terms of varying intrinsic efficacy and selective stabilization of receptor states with methods to detect and measure these effects. Last, the translation of in vitro to complex in vivo systems will be considered.</p>\",\"PeriodicalId\":12859,\"journal\":{\"name\":\"Handbook of experimental pharmacology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-10-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Handbook of experimental pharmacology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1007/164_2025_770\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"Pharmacology, Toxicology and Pharmaceutics\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Handbook of experimental pharmacology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1007/164_2025_770","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Pharmacology, Toxicology and Pharmaceutics","Score":null,"Total":0}
This chapter considers biased signaling as a natural function of G protein-coupled receptors (GPCRs) in the form of probe dependence. Thus, any ligand that changes the conformation of the receptor (agonist, antagonist, or allosteric modulator) has the potential to change the natural signaling of the receptor through unequal conformational alterations in the receptor structure. This gives an added dimension to agonist selectivity beyond extracellular recognition, namely the ability of agonists to emphasize certain signaling pathways in the cell at the expense of others. Given this, selectivity is discussed in terms of varying intrinsic efficacy and selective stabilization of receptor states with methods to detect and measure these effects. Last, the translation of in vitro to complex in vivo systems will be considered.
期刊介绍:
The Handbook of Experimental Pharmacology is one of the most authoritative and influential book series in pharmacology. It provides critical and comprehensive discussions of the most significant areas of pharmacological research, written by leading international authorities. Each volume in the series represents the most informative and contemporary account of its subject available, making it an unrivalled reference source.