LAUSR

Objectives: The dopaminergic and endothelin systems participate in the control of blood pressure by regulating sodium transport in the RPT. Both ETB receptor and D3 dopamine receptor exist in the RPTs; disruption of D3 or ETB receptor gene in mice produces hypertension. We hypothesize that the D3/ETB receptor interaction has a significant effect on sodium excretion in WKY rats, which may be impaired in SHRs. Methods: n this study, reagents were infused selectively into the right kidney of anesthetized WKY and SHRs. And D3 and ETB receptors expression were determined by immunoblot. The interaction between D3 and ETB receptors were checked by co-immunoprecipitation. Results: We found that a D3 receptor agonist (PD128907) induced natriuresis in WKY rats. An ETB receptor antagonist partially blocked the natriuretic effect of the D3 receptor agonist. In contrast, the effect of PD128907 on sodium excretion was impaired in SHRs. Study using laser confocal microscopy found that in the basal state in WKY cells, ETB receptor was confined mainly in the cell membrane. Treatment with PD128907 resulted in the internalization of ETB receptors and their intracellular co-localization with D3 receptors. Treatment with PD128907 in combination with ETB receptor antagonist failed to drive the ETB receptors intracellularly in WKY cells. In contrast, in SHR cells, the ETB receptors were found mainly in the cytoplasm under basal condition and thus were prevented from interacting with the agonist-stimulated, membrane-bound D3 receptors. Conclusion: We suggest that D3 receptors regulate RPT ETB receptors by physical receptor interaction and that the impaired natriuretic effect of D3 receptor in SHRs may be explained, in part, by an aberrant D3/ETB receptor interaction.