Renal D3 dopamine receptor stimulation induces natriuresis by endothelin B receptor interactions.
Dopaminergic and endothelin systems participate in the control blood pressure by regulating sodium transport in the renal proximal tubule. Disruption of either the endothelin B receptor (ETB) or D(3) dopamine receptor gene in mice produces hypertension. To examine whether these two receptors interact we studied the Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats by selectively infusing reagents into the right kidney of anesthetized rats. The D(3) receptor agonist (PD128907) caused natriuresis in WKY rats which was partially blocked by the ETB receptor antagonist. In contrast, PD128907 blunted sodium excretion in the SHRs. We found using laser confocal microscopy that the ETB receptor was mainly located in the cell membrane in control WKY cells. Treatment with the D(3) receptor antagonist caused its internalization into intracellular compartments that contained the D(3) receptors. Combined use of D(3) and ETB antagonists failed to internalize ETB receptors in cells from WKY rats. In contrast in SHR cells, ETB receptors were found mainly in internal compartments under basal condition and thus were likely prevented from interacting with the agonist-stimulated, membrane-bound D(3) receptors. Our studies suggest that D(3) receptors physically interact with proximal tubule ETB receptors and that the blunted natriuretic effect of dopamine in SHRs may be explained, in part, by abnormal D(3)/ETB receptor interactions.
Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, PR China.
Chunyu
C
Zeng
Laureano D
LD
Asico
Changqing
C
Yu
Van Anthony M
VA
Villar
Weibin
W
Shi
Yingjin
Y
Luo
Zheng
Z
Wang
Duofen
D
He
Yan
Y
Liu
Lan
L
Huang
Chengming
C
Yang
Xukai
X
Wang
Ulrich
U
Hopfer
Gilbert M
GM
Eisner
Pedro A
PA
Jose
D000818:Animals; D002462:Cell Membrane / Q000737:chemistry; D004705:Endocytosis; D065131:Endothelin B Receptor Antagonists; D007668:Kidney / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000737:chemistry; D009318:Natriuresis / Q000187:drug effects; D011485:Protein Binding; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044023:Receptor, Endothelin B / Q000032:analysis / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism*
D065131:Endothelin B Receptor Antagonists; D044023:Receptor, Endothelin B; D050637:Receptors, Dopamine D3