Adra1d, also known as the α1D-adrenergic receptor, is a key regulator of functions in the cardiovascular, prostate, and central nervous system. As a G-protein-coupled receptor, it is involved in pathways such as vasoconstriction, G protein-coupled amine receptor activity, and neuroactive ligand-receptor interaction [2,3]. It also has implications in glucocorticoid-related regulation, as well as in the regulation of calcium and adrenaline/noradrenaline signaling [4]. Genetic models are valuable for studying its function.

In cutaneous melanoma, overexpression of Adra1d in A375 melanoma cells and in a melanoma xenograft model in immunodeficient mice inhibited cell invasion, proliferation, and angiogenesis. This anti-angiogenic effect was achieved by negatively regulating the HIF-1α/VEGF axis [1]. In a study on vascular dementia, overexpression of Adra1d in PC12 cells subjected to oxygen-glucose deprivation decreased cell apoptosis, while silencing it increased apoptosis. The underlying mechanism involved regulation of phospholipase C beta (PLCβ) and inositol 1,4,5-trisphosphate receptor (IP3R) expression and intracellular Ca2+ levels [2]. In Dahl salt-sensitive hypertensive rats, treatment with QiShenYiQi down-regulated the expression of Adra1d in the kidney, which alleviated renal damage along with a reduction in blood pressure [5].

In conclusion, Adra1d is crucial for various physiological functions. Model-based research, especially through overexpression or silencing in cell lines and animal models, has revealed its role in diseases like cutaneous melanoma, vascular dementia, and hypertensive nephropathy. Understanding Adra1d can potentially offer new therapeutic strategies for these disease areas.

References:

1. Wang, Jianqiao, Ning, Danmei, Xie, Dong, Cao, Xianwei, Wan, Chuan. 2023. Functional Involvement of ADRA1D in Cutaneous Melanoma Progression and Angiogenesis. In Cellular and molecular biology (Noisy-le-Grand, France), 69, 44-50. doi:10.14715/cmb/2023.69.5.8. https://pubmed.ncbi.nlm.nih.gov/37571902/

2. Wu, Yuanhua, Cai, Jing, Pang, Bo, He, Qiansong, Zhang, Anbang. . Bioinformatic Identification of Signaling Pathways and Hub Genes in Vascular Dementia. In Actas espanolas de psiquiatria, 52, 83-98. doi:10.62641/aep.v52i2.1601. https://pubmed.ncbi.nlm.nih.gov/38622006/

3. Kountz, Timothy S, Lee, Kyung-Soon, Aggarwal-Howarth, Stacey, Scott, John D, Hague, Chris. 2016. Endogenous N-terminal Domain Cleavage Modulates α1D-Adrenergic Receptor Pharmacodynamics. In The Journal of biological chemistry, 291, 18210-21. doi:10.1074/jbc.M116.729517. https://pubmed.ncbi.nlm.nih.gov/27382054/

4. Juszczak, Grzegorz R, Stankiewicz, Adrian M. 2017. Glucocorticoids, genes and brain function. In Progress in neuro-psychopharmacology & biological psychiatry, 82, 136-168. doi:10.1016/j.pnpbp.2017.11.020. https://pubmed.ncbi.nlm.nih.gov/29180230/

5. Du, Hongxia, Xiao, Guangxu, Xue, Zhifeng, Wang, Xiaoying, Zhu, Yan. 2021. QiShenYiQi ameliorates salt-induced hypertensive nephropathy by balancing ADRA1D and SIK1 expression in Dahl salt-sensitive rats. In Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 141, 111941. doi:10.1016/j.biopha.2021.111941. https://pubmed.ncbi.nlm.nih.gov/34328102/