| dbo:abstract |
Funktionelle Selektivität bezeichnet in der Pharmakologie das Phänomen, dass biologisch wirksame Substanzen (Wirkstoffe, Liganden) nach deren Bindung an einen Rezeptor bevorzugt einen von mehreren möglichen Signaltransduktionswegen aktivieren können. Dieses Phänomen kann prinzipiell an allen Rezeptoren beobachtet werden, die mindestens zwei verschiedene Signaltransduktionswege gekoppelt sind. Funktionelle Selektivität konnte für verschiedene Liganden an und G-Protein-gekoppelten Rezeptoren beobachtet werden. Die Beobachtung einer funktionellen Selektivität eines Liganden kann dabei kausal auf die Unterschiedlichkeit der untersuchten Effekte (z. B. schnell oder langsam einsetzende Effekte), unterschiedlich starke Expression und Aktivität des Rezeptorproteins oder auf Eigenschaften des Liganden selbst zurückgeführt werden. Im letzteren Fall spricht man auch von biased agonism, agonist-selective trafficking of stimulus oder ligand-selective agonism. (de) Functional selectivity (or “agonist trafficking”, “biased agonism”, “biased signaling”, "ligand bias" and “differential engagement”) is the ligand-dependent selectivity for certain signal transduction pathways relative to a reference ligand (often the endogenous hormone or peptide) at the same receptor. Functional selectivity can be present when a receptor has several possible signal transduction pathways. To which degree each pathway is activated thus depends on which ligand binds to the receptor. Functional selectivity, or biased signaling, is most extensively characterized at G protein coupled receptors (GPCRs). A number of biased agonists, such as those at muscarinic M2 receptors tested as analgesics or antiproliferative drugs, or those at opioid receptors that mediate pain, show potential at various receptor families to increase beneficial properties while reducing side effects. For example, pre-clinical studies with G protein biased agonists at the μ-opioid receptor show equivalent efficacy for treating pain with reduced risk for addictive potential and respiratory depression. Studies within the chemokine receptor system also suggest that GPCR biased agonism is physiologically relevant. For example, a beta-arrestin biased agonist of the chemokine receptor CXCR3 induced greater chemotaxis of T cells relative to a G protein biased agonist. (en) |
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Funktionelle Selektivität bezeichnet in der Pharmakologie das Phänomen, dass biologisch wirksame Substanzen (Wirkstoffe, Liganden) nach deren Bindung an einen Rezeptor bevorzugt einen von mehreren möglichen Signaltransduktionswegen aktivieren können. Dieses Phänomen kann prinzipiell an allen Rezeptoren beobachtet werden, die mindestens zwei verschiedene Signaltransduktionswege gekoppelt sind. Funktionelle Selektivität konnte für verschiedene Liganden an und G-Protein-gekoppelten Rezeptoren beobachtet werden. (de) Functional selectivity (or “agonist trafficking”, “biased agonism”, “biased signaling”, "ligand bias" and “differential engagement”) is the ligand-dependent selectivity for certain signal transduction pathways relative to a reference ligand (often the endogenous hormone or peptide) at the same receptor. Functional selectivity can be present when a receptor has several possible signal transduction pathways. To which degree each pathway is activated thus depends on which ligand binds to the receptor. Functional selectivity, or biased signaling, is most extensively characterized at G protein coupled receptors (GPCRs). A number of biased agonists, such as those at muscarinic M2 receptors tested as analgesics or antiproliferative drugs, or those at opioid receptors that mediate pain, show poten (en) |
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