Crosstalk between dopamine receptors and the Na+/K+‑ATPase (Review)

Zhang,Li‑Nan; Li,Jun‑Xia; Hao,Liang; Sun,Yong‑Jun; Xie,Ying‑Hua; Wu,Shao‑Mei; Liu,Lei; Chen,Xiao-Long; Gao,Zi-Bin

doi:10.3892/mmr.2013.1697

Crosstalk between dopamine receptors and the Na+/K+‑ATPase (Review)

Authors:
- Li‑Nan Zhang
- Jun‑Xia Li
- Liang Hao
- Yong‑Jun Sun
- Ying‑Hua Xie
- Shao‑Mei Wu
- Lei Liu
- Xiao-Long Chen
- Zi-Bin Gao
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Affiliations: Department of Pharmacy, College of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, Shijiazhuang, Hebei 050018, P.R. China, Department of Pharmacology, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China, Department of Neurosurgery, Third Hospital of Shijiazhuang, Shijiazhuang, Hebei 050011, P.R. China
Published online on: September 19, 2013 https://doi.org/10.3892/mmr.2013.1697
Pages: 1291-1299

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Abstract

Dopamine (DA) receptors, which belong to the G protein‑coupled receptor family, are the target of ~50% of all modern medicinal drugs and constitute a large and diverse class of proteins whose primary function is to transduce extracellular stimuli into intracellular signals. Na+/K+‑ATPase (NKA) is ubiquitous and crucial for the maintenance of intracellular ion homeostasis and excitability. Furthermore, it plays a critical role in diverse effects, including clinical cardiotonic and cardioprotective effects, ischemic preconditioning in the brain, natriuresis, lung edema clearance and other processes. NKA regulation is of physiological and pharmacological importance and has species‑ and tissue‑specific variations. The activation of DA receptors regulates NKA expression/activity and trafficking in various tissues and cells, for example in the kidney, lung, intestine, brain, non‑pigmented ciliary epithelium and the vascular bed. DA receptor‑mediated regulation of NKA mediates a diverse range of cellular responses and includes endocytosis/exocytosis, phosphorylation/dephosphorylation of the α subunit of NKA and multiple signaling pathways, including phosphatidylinositol (PI)‑phospholipase C/protein kinase (PK) C, cAMP/PKA, PI3K, adaptor protein 2, tyrosine phosphatase and mitogen‑activated protein kinase/extracellular signal‑regulated protein kinase. Furthermore, in brain and HEK293T cells, D1 and D2 receptors exist in a complex with NKA. Among D1 and D2 receptors and NKA, regulations are reciprocal, which leads to crosstalk between DA receptors and NKA. In the present study, the current understanding of signaling mechanisms responsible for the crosstalk between DA receptors and NKA, as well as with specific consequent functions, is reviewed.

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