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Effect of D(4) Dopamine Receptor on Na(+)-K(+)-ATPase Activity in Renal Proximal Tubule Cells
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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Lippincott Williams & Wilkins
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10030170/ https://www.ncbi.nlm.nih.gov/pubmed/36969984 http://dx.doi.org/10.1097/CD9.0000000000000076 |
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author | He, Duofen Ren, Hongmei Wang, Hongyong Jose, Pedro A. Zeng, Chunyu Xia, Tianyang Yang, Jian |
author_facet | He, Duofen Ren, Hongmei Wang, Hongyong Jose, Pedro A. Zeng, Chunyu Xia, Tianyang Yang, Jian |
author_sort | He, Duofen |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10030170 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-100301702023-03-22 Effect of D(4) Dopamine Receptor on Na(+)-K(+)-ATPase Activity in Renal Proximal Tubule Cells He, Duofen Ren, Hongmei Wang, Hongyong Jose, Pedro A. Zeng, Chunyu Xia, Tianyang Yang, Jian Cardiol Discov Original Articles 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. Lippincott Williams & Wilkins 2022-10-14 2023-03 /pmc/articles/PMC10030170/ /pubmed/36969984 http://dx.doi.org/10.1097/CD9.0000000000000076 Text en Copyright © 2022 The Chinese Medical Association, published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. |
spellingShingle | Original Articles He, Duofen Ren, Hongmei Wang, Hongyong Jose, Pedro A. Zeng, Chunyu Xia, Tianyang Yang, Jian Effect of D(4) Dopamine Receptor on Na(+)-K(+)-ATPase Activity in Renal Proximal Tubule Cells |
title | Effect of D(4) Dopamine Receptor on Na(+)-K(+)-ATPase Activity in Renal Proximal Tubule Cells |
title_full | Effect of D(4) Dopamine Receptor on Na(+)-K(+)-ATPase Activity in Renal Proximal Tubule Cells |
title_fullStr | Effect of D(4) Dopamine Receptor on Na(+)-K(+)-ATPase Activity in Renal Proximal Tubule Cells |
title_full_unstemmed | Effect of D(4) Dopamine Receptor on Na(+)-K(+)-ATPase Activity in Renal Proximal Tubule Cells |
title_short | Effect of D(4) Dopamine Receptor on Na(+)-K(+)-ATPase Activity in Renal Proximal Tubule Cells |
title_sort | effect of d(4) dopamine receptor on na(+)-k(+)-atpase activity in renal proximal tubule cells |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10030170/ https://www.ncbi.nlm.nih.gov/pubmed/36969984 http://dx.doi.org/10.1097/CD9.0000000000000076 |
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