Development of a genetically encoded sensor for probing endogenous nociceptin opioid peptide release.

Autor: Zhou X; Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland.; Neuroscience Center Zurich, University and ETH Zürich, Zürich, Switzerland., Stine C; Center for the Neurobiology of Addiction, Pain, and Emotion, University of Washington, Seattle, WA, USA.; Departments of Anesthesiology and Pharmacology and Bioengineering, University of Washington, Seattle, WA, USA.; Molecular and Cellular Biology, University of Washington School of Medicine, Seattle, WA, USA., Prada PO; Max Planck Institute for Metabolism Research, Cologne, Germany.; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.; School of Applied Sciences, State University of Campinas (UNICAMP), Limeira, Sao Paulo, Brazil., Fusca D; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.; Institute of Zoology, Department of Biology, University of Cologne, Cologne, Germany., Assoumou K; Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland., Dernic J; Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland., Bhat MA; Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland., Achanta AS; Center for the Neurobiology of Addiction, Pain, and Emotion, University of Washington, Seattle, WA, USA.; Departments of Anesthesiology and Pharmacology and Bioengineering, University of Washington, Seattle, WA, USA., Johnson JC; Center for the Neurobiology of Addiction, Pain, and Emotion, University of Washington, Seattle, WA, USA.; Departments of Anesthesiology and Pharmacology and Bioengineering, University of Washington, Seattle, WA, USA., Pasqualini AL; Center for the Neurobiology of Addiction, Pain, and Emotion, University of Washington, Seattle, WA, USA.; Departments of Anesthesiology and Pharmacology and Bioengineering, University of Washington, Seattle, WA, USA., Jadhav S; Center for the Neurobiology of Addiction, Pain, and Emotion, University of Washington, Seattle, WA, USA.; Departments of Anesthesiology and Pharmacology and Bioengineering, University of Washington, Seattle, WA, USA., Bauder CA; Max Planck Institute for Metabolism Research, Cologne, Germany.; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany., Steuernagel L; Max Planck Institute for Metabolism Research, Cologne, Germany.; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany., Ravotto L; Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland., Benke D; Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland.; Neuroscience Center Zurich, University and ETH Zürich, Zürich, Switzerland., Weber B; Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland.; Neuroscience Center Zurich, University and ETH Zürich, Zürich, Switzerland., Suko A; Center for the Neurobiology of Addiction, Pain, and Emotion, University of Washington, Seattle, WA, USA.; Departments of Anesthesiology and Pharmacology and Bioengineering, University of Washington, Seattle, WA, USA., Palmiter RD; Center for the Neurobiology of Addiction, Pain, and Emotion, University of Washington, Seattle, WA, USA.; Howard Hughes Medical Institute and Departments of Biochemistry and Genome Sciences, University of Washington, Seattle, WA, 98195, USA., Stoeber M; Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland., Kloppenburg P; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.; Institute of Zoology, Department of Biology, University of Cologne, Cologne, Germany., Brüning JC; Max Planck Institute for Metabolism Research, Cologne, Germany.; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.; Policlinic for Endocrinology, Diabetes and Preventive Medicine (PEDP), University Hospital Cologne, Cologne, Germany., Bruchas MR; Center for the Neurobiology of Addiction, Pain, and Emotion, University of Washington, Seattle, WA, USA. mbruchas@uw.edu.; Departments of Anesthesiology and Pharmacology and Bioengineering, University of Washington, Seattle, WA, USA. mbruchas@uw.edu.; Molecular and Cellular Biology, University of Washington School of Medicine, Seattle, WA, USA. mbruchas@uw.edu., Patriarchi T; Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland. patriarchi@pharma.uzh.ch.; Neuroscience Center Zurich, University and ETH Zürich, Zürich, Switzerland. patriarchi@pharma.uzh.ch.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Jun 25; Vol. 15 (1), pp. 5353. Date of Electronic Publication: 2024 Jun 25.
DOI: 10.1038/s41467-024-49712-0
Abstrakt: Nociceptin/orphanin-FQ (N/OFQ) is a recently appreciated critical opioid peptide with key regulatory functions in several central behavioral processes including motivation, stress, feeding, and sleep. The functional relevance of N/OFQ action in the mammalian brain remains unclear due to a lack of high-resolution approaches to detect this neuropeptide with appropriate spatial and temporal resolution. Here we develop and characterize NOPLight, a genetically encoded sensor that sensitively reports changes in endogenous N/OFQ release. We characterized the affinity, pharmacological profile, spectral properties, kinetics, ligand selectivity, and potential interaction with intracellular signal transducers of NOPLight in vitro. Its functionality was established in acute brain slices by exogeneous N/OFQ application and chemogenetic induction of endogenous N/OFQ release from PNOC neurons. In vivo studies with fibre photometry enabled direct recording of NOPLight binding to exogenous N/OFQ receptor ligands, as well as detection of endogenous N/OFQ release within the paranigral ventral tegmental area (pnVTA) during natural behaviors and chemogenetic activation of PNOC neurons. In summary, we show here that NOPLight can be used to detect N/OFQ opioid peptide signal dynamics in tissue and freely behaving animals.
(© 2024. The Author(s).)
Databáze: MEDLINE
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