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

Overview

Journal Cardiol Discov

Date 2023 Mar 27

PMID 36969984

Authors

Duofen He

Hongmei Ren

Hongyong Wang

Pedro A Jose

Chunyu Zeng

Tianyang Xia

Jian Yang

Affiliations

Soon will be listed here.

Abstract

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.

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