Negative reciprocity between angiotensin II type 1 and dopamine D1 receptors in rat renal proximal tubule cells.
Sodium excretion is bidirectionally regulated by dopamine, acting on D1-like receptors (D1R) and angiotensin II, acting on AT1 receptors (AT1R). Since sodium excretion has to be regulated with great precision within a short frame of time, we tested the short-term effects of agonist binding on the function of the reciprocal receptor within the D1R-AT1R complex in renal proximal tubule cells. Exposure of rat renal proximal tubule cells to a D1 agonist was found to result in a rapid partial internalization of AT1R and complete abolishment of AT1R signaling. Similarly, exposure of rat proximal tubule cells and renal tissue to angiotensin II resulted in a rapid partial internalization of D1R and abolishment of D1R signaling. D1R and AT1R were, by use of coimmunoprecipitation studies and glutathione-S-transferase pull-down assays, shown to be partners in a multiprotein complex. Na+-K+-ATPase, the target for both receptors, was included in this complex, and a region in the COOH-terminal tail of D1R (residues 397-416) was found to interact with both AT1R and Na+-K+-ATPase. Results indicate that AT1R and D1R function as a unit of opposites, which should provide a highly versatile and sensitive system for short-term regulation of sodium excretion.
Khan
Farah
F
Department of Woman and Child Health, Karolinska Institutet, Astrid Lindgren Children's Hospital, Q2:09, SE-171 76 Stockholm, Sweden.
Spicarová
Zuzana
Z
Zelenin
Sergey
S
Holtbäck
Ulla
U
Scott
Lena
L
Aperia
Anita
A
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D017434:Protein Structure, Tertiary; D051381:Rats; D017207:Rats, Sprague-Dawley; D020239:Receptor Cross-Talk / Q000502:physiology; D044140:Receptor, Angiotensin, Type 1 / Q000819:agonists / Q000737:chemistry / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000737:chemistry / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D001552:Benzazepines; D018491:Dopamine Agonists; D044140:Receptor, Angiotensin, Type 1; D017447:Receptors, Dopamine D1; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C067113:SK&F 81297; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase