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Functional Selectivity of Dopamine D(1) Receptor Signaling: Retrospect and Prospect
Research progress on dopamine D(1) receptors indicates that signaling no longer is limited to G protein-dependent cyclic adenosine monophosphate phosphorylation but also includes G protein-independent β-arrestin-related mitogen-activated protein kinase activation, regulation of ion channels, phospho...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584964/ https://www.ncbi.nlm.nih.gov/pubmed/34769344 http://dx.doi.org/10.3390/ijms222111914 |
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author | Yang, Yang |
author_facet | Yang, Yang |
author_sort | Yang, Yang |
collection | PubMed |
description | Research progress on dopamine D(1) receptors indicates that signaling no longer is limited to G protein-dependent cyclic adenosine monophosphate phosphorylation but also includes G protein-independent β-arrestin-related mitogen-activated protein kinase activation, regulation of ion channels, phospholipase C activation, and possibly more. This review summarizes recent studies revealing the complexity of D(1) signaling and its clinical implications, and suggests functional selectivity as a promising strategy for drug discovery to magnify the merit of D(1) signaling. Functional selectivity/biased receptor signaling has become a major research front because of its potential to improve therapeutics through precise targeting. Retrospective pharmacological review indicated that many D(1) ligands have some degree of mild functional selectivity, and novel compounds with extreme bias at D(1) signaling were reported recently. Behavioral and neurophysiological studies inspired new methods to investigate functional selectivity and gave insight into the biased signaling of several drugs. Results from recent clinical trials also supported D(1) functional selectivity signaling as a promising strategy for discovery and development of better therapeutics. |
format | Online Article Text |
id | pubmed-8584964 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85849642021-11-12 Functional Selectivity of Dopamine D(1) Receptor Signaling: Retrospect and Prospect Yang, Yang Int J Mol Sci Review Research progress on dopamine D(1) receptors indicates that signaling no longer is limited to G protein-dependent cyclic adenosine monophosphate phosphorylation but also includes G protein-independent β-arrestin-related mitogen-activated protein kinase activation, regulation of ion channels, phospholipase C activation, and possibly more. This review summarizes recent studies revealing the complexity of D(1) signaling and its clinical implications, and suggests functional selectivity as a promising strategy for drug discovery to magnify the merit of D(1) signaling. Functional selectivity/biased receptor signaling has become a major research front because of its potential to improve therapeutics through precise targeting. Retrospective pharmacological review indicated that many D(1) ligands have some degree of mild functional selectivity, and novel compounds with extreme bias at D(1) signaling were reported recently. Behavioral and neurophysiological studies inspired new methods to investigate functional selectivity and gave insight into the biased signaling of several drugs. Results from recent clinical trials also supported D(1) functional selectivity signaling as a promising strategy for discovery and development of better therapeutics. MDPI 2021-11-03 /pmc/articles/PMC8584964/ /pubmed/34769344 http://dx.doi.org/10.3390/ijms222111914 Text en © 2021 by the author. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Yang, Yang Functional Selectivity of Dopamine D(1) Receptor Signaling: Retrospect and Prospect |
title | Functional Selectivity of Dopamine D(1) Receptor Signaling: Retrospect and Prospect |
title_full | Functional Selectivity of Dopamine D(1) Receptor Signaling: Retrospect and Prospect |
title_fullStr | Functional Selectivity of Dopamine D(1) Receptor Signaling: Retrospect and Prospect |
title_full_unstemmed | Functional Selectivity of Dopamine D(1) Receptor Signaling: Retrospect and Prospect |
title_short | Functional Selectivity of Dopamine D(1) Receptor Signaling: Retrospect and Prospect |
title_sort | functional selectivity of dopamine d(1) receptor signaling: retrospect and prospect |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584964/ https://www.ncbi.nlm.nih.gov/pubmed/34769344 http://dx.doi.org/10.3390/ijms222111914 |
work_keys_str_mv | AT yangyang functionalselectivityofdopamined1receptorsignalingretrospectandprospect |