Effect of D 4 Dopamine Receptor on Na +-K +-ATPase Activity in Renal Proximal Tubule Cells
10.1097/CD9.0000000000000076
- VernacularTitle:Effect of D 4 Dopamine Receptor on Na +-K +-ATPase Activity in Renal Proximal Tubule Cells
- Author:
Duofen HE
1
;
Hongmei REN
;
Hongyong WANG
;
Jose Pedro A.
;
Chunyu ZENG
;
Tianyang XIA
;
Jian YANG
Author Information
1. Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China
- Publication Type:Journal Article
- Keywords:
Sodium-potassium-exchanging ATPase;
Dopamine D 4 receptor;
Renal proximal tubule;
Kidney;
Hypertension
- From:
Cardiology Discovery
2023;03(1):24-29
- CountryChina
- Language:English
-
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.
