TY - JOUR
T1 - Dopamine D1 receptor-mediated β-arrestin signaling
T2 - Insight from pharmacology, biology, behavior, and neurophysiology
AU - Yang, Yang
AU - Lewis, Mechelle M.
AU - Huang, Xuemei
AU - Dokholyan, Nikolay V.
AU - Mailman, Richard B.
N1 - Publisher Copyright:
© 2022 Elsevier Ltd
PY - 2022/7
Y1 - 2022/7
N2 - The awareness of the potential importance of functional selectivity/biased signaling has led to the discovery of biased compounds as both research tools and novel drugs. A major pan-receptor focus has been to identify GPCR-selective ligands that have bias in G protein-dependent vs. β-arrestin related signaling. Although this field has exploded during the past two decades, it is only recently that highly β-arrestin biased ligands for the dopamine D1 receptor were reported. We now summarize important pharmacological, molecular, and cellular studies relevant to D1-mediated β-arrestin-related signaling. It is intriguing that many results emerged from behavioral and physiological studies implying that bias toward or against D1-mediated β-arrestin either can improve or impair functional outcomes. We discuss the importance of understanding the translatability of cell and animal models to have more precise functional targeting to harness the value of this signaling pathway.
AB - The awareness of the potential importance of functional selectivity/biased signaling has led to the discovery of biased compounds as both research tools and novel drugs. A major pan-receptor focus has been to identify GPCR-selective ligands that have bias in G protein-dependent vs. β-arrestin related signaling. Although this field has exploded during the past two decades, it is only recently that highly β-arrestin biased ligands for the dopamine D1 receptor were reported. We now summarize important pharmacological, molecular, and cellular studies relevant to D1-mediated β-arrestin-related signaling. It is intriguing that many results emerged from behavioral and physiological studies implying that bias toward or against D1-mediated β-arrestin either can improve or impair functional outcomes. We discuss the importance of understanding the translatability of cell and animal models to have more precise functional targeting to harness the value of this signaling pathway.
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U2 - 10.1016/j.biocel.2022.106235
DO - 10.1016/j.biocel.2022.106235
M3 - Short survey
C2 - 35688404
AN - SCOPUS:85131768935
SN - 1357-2725
VL - 148
JO - International Journal of Biochemistry and Cell Biology
JF - International Journal of Biochemistry and Cell Biology
M1 - 106235
ER -