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

Authors

Duofen He, Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China.
Hongmei Ren, Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China.
Hongyong Wang, Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China.
Pedro A. Jose, 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.
Chunyu Zeng, Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China.
Tianyang Xia, Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China.
Jian Yang, Research Center for Metabolic and Cardiovascular Diseases, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 410020, China.

Document Type

Journal Article

Publication Date

3-1-2023

Journal

Cardiology discovery

Volume

3

Issue

1

DOI

10.1097/CD9.0000000000000076

Keywords

Dopamine D4 receptor; Hypertension; Kidney; Renal proximal tubule; Sodium-potassium-exchanging ATPase

Abstract

UNLABELLED: 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 dopamine receptor (D receptor) in renal proximal tubules (PRTs) is still unclear. This study aimed to verify the hypothesis that activation of D 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 receptor agonist PD168077 and/or the D 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 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 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 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 receptors also increased NO levels in the culture medium and cGMP levels in RPT cells. However, the inhibitory effect of D receptors on NKA activity was absent in RPT cells from SHRs, which could be related to decreased plasma membrane expression of D receptors in SHR RPT cells. CONCLUSIONS: Activation of D 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.

APA Citation

He, Duofen; Ren, Hongmei; Wang, Hongyong; Jose, Pedro A.; Zeng, Chunyu; Xia, Tianyang; and Yang, Jian, "Effect of D Dopamine Receptor on Na-K-ATPase Activity in Renal Proximal Tubule Cells" (2023). GW Authored Works. Paper 2628.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/2628

Department

Medicine