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other·preclinical research, biomedical research, nephrology, cardiology·PMC10030170

Effect of D 4 Dopamine Receptor on Na + -K + -ATPase Activity in Renal Proximal Tubule Cells

Cardiology Discovery · 7 authors, 5 centres

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TL;DR

D4 receptor activation inhibited NKA activity via the NO/cGMP signaling pathway in WKY rat cells but not in SHR cells.

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Activation of D4 receptors with PD168077 inhibited NKA activity in WKY RPT cells in a concentration- and time-dependent manner, an effect prevented by the D4 antagonist L745870. The NO synthase inhibitor L-NAME and soluble guanylyl cyclase inhibitor ODQ blocked the inhibitory effect of PD168077, implicating the NO/cGMP signaling pathway. Both NO and cGMP levels increased after D4 receptor activation. The inhibitory effect of D4 receptors on NKA activity was absent in SHR RPT cells, despite higher total D4 receptor expression, which appeared related to decreased plasma membrane expression of D4 receptors.

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other

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preclinical research

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100% · A

ORIGINAL PAPER

PMC10030170

Effect of D 4 Dopamine Receptor on Na + -K + -ATPase Activity in Renal Proximal Tubule Cells

Cardiology Discovery

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ABSTRACT

Objective: Dopamine, via its receptors, plays a vital role in the maintenance of blood pressure by modulating renal sodium transport. However, the role of the D 4 dopamine receptor (D 4 receptor) in renal proximal tubules (PRTs) is still unclear. This study aimed to verify the hypothesis that activation of D 4 receptor directly inhibits the activity of the Na + -K + -ATPase (NKA) in RPT cells. Methods: NKA activity, nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) levels were measured in RPT cells treated with the D 4 receptor agonist PD168077 and/or the D 4 receptor antagonist L745870, the NO synthase inhibitor NG-nitro-L-arginine-methyl ester (L-NAME) or the soluble guanylyl cyclase inhibitor 1H-[1,2,4] oxadiazolo-[4,3-a] quinoxalin-1-one (ODQ). Total D 4 receptor expression and its expression in the plasma membrane were investigated by immunoblotting in RPT cells from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Results: Activation of D 4 receptors with PD168077 , inhibited NKA activity in RPT cells from WKY rats in a concentration- and time-dependent manner. The inhibitory effect of PD168077 on NKA activity was prevented by the addition of the D 4 receptor antagonist L745870, which by itself had no effect. The NO synthase inhibitor L-NAME and the soluble guanylyl cyclase inhibitor ODQ, which by themselves had no effect on NKA activity, eliminated the inhibitory effect of PD168077 on NKA activity. Activation of D 4 receptors also increased NO levels in the culture medium and cGMP levels in RPT cells. However, the inhibitory effect of D 4 receptors on NKA activity was absent in RPT cells from SHRs, which could be related to decreased plasma membrane expression of D 4 receptors in SHR RPT cells. Conclusions: Activation of D 4 receptors directly inhibits NKA activity via the NO/cGMP signaling pathway in RPT cells from WKY rats but not SHRs. Aberrant regulation of NKA activity in RPT cells may be involved in the pathogenesis of hypertension.

CITATION EXPORT

Duofen He, Hongmei Ren, Hongyong Wang et al.. Effect of D4 Dopamine Receptor on Na+-K+-ATPase Activity in Renal Proximal Tubule Cells. Cardiology Discovery. (2022). https://doi.org/10.1097/CD9.0000000000000076

AUTHORS

7 · 5 CENTRES

Duofen He, Hongmei Ren, Hongyong Wang, Pedro A. Jose, Chunyu Zeng, Tianyang Xia, Jian Yang

1 Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China
2 Chongqing Institute of Cardiology & Chongqing Key Laboratory of Hypertension Research, Chongqing 400042, China
3 Division of Renal Diseases & Hypertension, Department of Medicine and Department of Physiology and Pharmacology, The George Washington University School of Medicine & Health Sciences, Washington, District of Columbia 20052, USA
4 Research Center for Metabolic and Cardiovascular Diseases, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 410020, China
5 Department of Clinical Nutrition, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 410020, China.