D3 Dopamine receptor regulation of ETB receptors in renal proximal tubule cells from WKY and SHRS

Document Type

Journal Article

Publication Date

8-1-2009

Journal

American Journal of Hypertension

Volume

22

Issue

8

DOI

10.1038/ajh.2009.80

Abstract

BackgroundThe dopaminergic and endothelin systems, by regulating sodium transport in the renal proximal tubule (RPT), participate in the control of blood pressure. The D3 and ETB receptors are expressed in RPTs, and D3 receptor function in RPTs is impaired in spontaneously hypertensive rats (SHRs). Therefore, we tested the hypothesis that D3 receptors can regulate ETB receptors, and that D3 receptor regulation of ETB receptors in RPTs is impaired in SHRs.MethodsETB receptor expression in RPT cells was measured by immunoblotting and reverse transcriptase-PCR and ETB receptor function by measuring Na+-K + ATPase activity. D3 /ETB receptor interaction was studied by co-immunoprecipitation.ResultsIn Wistar-Kyoto (WKY) RPT cells, the D3 receptor agonist, PD128907, increased ETB receptor protein expression, effects that were blocked by removal of calcium in the culture medium. The stimulatory effect of D3 on ETB receptor mRNA and protein expression was also blocked by nicardipine. In contrast, in SHR RPT cells, PD128907 decreased ETB receptor expression. Basal D3 /ETB receptor co-immunoprecipitation was three times greater in WKY than in SHRs. The absolute amount of D3 /ETB receptor co-immunoprecipitation induced by a D3 receptor agonist was also greater in WKY than in SHRs. Stimulation of ETB receptors decreased Na+-K+ ATPase activity in WKY but not in SHR cells. Pretreatment with PD128907 augmented the inhibitory effect of BQ3020 on Na+-K+ ATPase activity in WKY but not in SHR cells.Conclusions D3 receptors regulate ETB receptors by physical receptor interaction and govern receptor expression and function. D3 receptor regulation of ETB receptors is aberrant in RPT cells from SHRs. © 2009 American Journal of Hypertension, Ltd.

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