Trends in Pharmacological Sciences
PrinciplesAgonist-receptor efficacy I: mechanisms of efficacy and receptor promiscuity
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Cited by (179)
Receptors: Opioid receptors
2021, Encyclopedia of Biological Chemistry: Third EditionDopamine requires unique residues to signal via the serotonin 2A receptor
2020, NeuroscienceCitation Excerpt :This is accepted as the canonical signaling pathway of the receptor. Some GPCRs display a phenomenon referred to as “functional selectivity” or “ligand biased agonism”, which is characterized by ligands binding to the receptor, activating downstream pathways or/and modulating intracellular transduction cascades differentially (Kenakin, 1995a,b; Urban et al., 2007). This functional selectivity possibly arises out of “GPCR pleiotropy”, or the “structural flexibility” of a receptor to occupy a particular conformation space biased by the interacting ligand, which may or may not be different from the steady-state conformation space (Kenakin, 2004; Abrol et al., 2013).
Functional selectivity and dualsteric/bitopic GPCR targeting
2017, Current Opinion in PharmacologySerotonin-2A homodimers are needed for signalling via both phospholipase A<inf>2</inf> and phospholipase C in transfected CHO cells
2017, European Journal of PharmacologyLigand-selective activation of heterologously-expressed mammalian olfactory receptor
2014, Cell CalciumCitation Excerpt :G-protein coupled receptors (GPCRs) can show a hierarchy of downstream signaling imposed primarily by the conformational stage of the ligand-GPCR complex, such that different ligands reproducibly shift the balance of the cell's signaling network towards different transduction pathways. This concept, originally introduced in the 1990s [1–3] and most commonly referred to as ligand induced selective signaling or biased agonism, has since become a well-recognized phenomenon of significance to both basic and clinical science [4–6]. Mechanisms mediating ligand selective signaling can be complex, including processes such as activation of multiple G-protein isoforms [7], β-arrestins [8], the heteromerization of GPCRs [6], and direct interaction of GPCR and G-protein subunits with a variety of ion channels, including Ca2+ channels [9,10] and G-protein-gated inwardly rectifying potassium channels, GIRKs [11], among others.