Functional Selectivity of Dopamine D<sub>1</sub> Receptor Signaling: Retrospect and Prospect

Research progress on dopamine D<sub>1</sub> 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...

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Autor principal:	Yang Yang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	functional selectivity dopamine D<sub>1</sub> receptor clinical implications Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/57ca4d33730448d39a2573e6b70671f5
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spelling	oai:doaj.org-article:57ca4d33730448d39a2573e6b70671f52021-11-11T17:19:43ZFunctional Selectivity of Dopamine D<sub>1</sub> Receptor Signaling: Retrospect and Prospect10.3390/ijms2221119141422-00671661-6596https://doaj.org/article/57ca4d33730448d39a2573e6b70671f52021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11914https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Research progress on dopamine D<sub>1</sub> 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<sub>1</sub> signaling and its clinical implications, and suggests functional selectivity as a promising strategy for drug discovery to magnify the merit of D<sub>1</sub> 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<sub>1</sub> ligands have some degree of mild functional selectivity, and novel compounds with extreme bias at D<sub>1</sub> 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<sub>1</sub> functional selectivity signaling as a promising strategy for discovery and development of better therapeutics.Yang YangMDPI AGarticlefunctional selectivitydopamine D<sub>1</sub> receptorclinical implicationsBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11914, p 11914 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	functional selectivity dopamine D<sub>1</sub> receptor clinical implications Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	functional selectivity dopamine D<sub>1</sub> receptor clinical implications Biology (General) QH301-705.5 Chemistry QD1-999 Yang Yang Functional Selectivity of Dopamine D<sub>1</sub> Receptor Signaling: Retrospect and Prospect
description	Research progress on dopamine D<sub>1</sub> 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<sub>1</sub> signaling and its clinical implications, and suggests functional selectivity as a promising strategy for drug discovery to magnify the merit of D<sub>1</sub> 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<sub>1</sub> ligands have some degree of mild functional selectivity, and novel compounds with extreme bias at D<sub>1</sub> 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<sub>1</sub> functional selectivity signaling as a promising strategy for discovery and development of better therapeutics.
format	article
author	Yang Yang
author_facet	Yang Yang
author_sort	Yang Yang
title	Functional Selectivity of Dopamine D<sub>1</sub> Receptor Signaling: Retrospect and Prospect
title_short	Functional Selectivity of Dopamine D<sub>1</sub> Receptor Signaling: Retrospect and Prospect
title_full	Functional Selectivity of Dopamine D<sub>1</sub> Receptor Signaling: Retrospect and Prospect
title_fullStr	Functional Selectivity of Dopamine D<sub>1</sub> Receptor Signaling: Retrospect and Prospect
title_full_unstemmed	Functional Selectivity of Dopamine D<sub>1</sub> Receptor Signaling: Retrospect and Prospect
title_sort	functional selectivity of dopamine d<sub>1</sub> receptor signaling: retrospect and prospect
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/57ca4d33730448d39a2573e6b70671f5
work_keys_str_mv	AT yangyang functionalselectivityofdopaminedsub1subreceptorsignalingretrospectandprospect
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Functional Selectivity of Dopamine D<sub>1</sub> Receptor Signaling: Retrospect and Prospect

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