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Dopamine 4 receptor regulates sodium chloride cotransporter in renal distal convoluted tubular cells
Author(s) -
Upadhyay Kiran,
Jose Pedro,
Wang Xiaoyan
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1041.9
Subject(s) - distal convoluted tubule , agonist , chemistry , endocrinology , medicine , cotransporter , receptor , sodium , antagonist , reabsorption , biology , biochemistry , organic chemistry
Dopamine 4 receptor (D4R) plays an important role in the regulation of renal sodium (Na) transport and hence blood pressure. We hypothesized that D4R inhibits Na transport in the distal convoluted tubule (DCT) by interacting with thiazide–sensitive sodium chloride cotransporter (NCC). We measured NCC activity and expression in immortalized mouse DCT cells in response to D4R agonist/antagonist. D4R and NCC were co‐localized in the plasma membrane as observed by immunofluorescence laser confocal microscopy. The two proteins were also co‐immunoprecipitated. In polarized DCT cells, D4R agonist (PD168077, 10μM, 1hr) decreased a chloride‐dependent Na transport by 26±1% (n=7), similar to thiazide (Metolazone, 10μM) with 29±1% (n=7) inhibition, as measured by intracellular Na + content. D4R antagonist (L‐745,870, 1μM) alone had no effect but partially blocked the agonist‐mediated inhibition on Na + transport. D4R agonist (10μM, 24 hrs) also decreased NCC protein expression (western blot) by 53± 6% (n=6). Cell proliferation and viability were not affected by the D4R agonist/antagonist. In D4R −/− mice, the protein expression of renal NCC was increased (D4 +/+:100±10%, D4 −/−:209±38%, n=5), in agreement with our previous report. We conclude that D4R may directly inhibit the function and protein expression of NCC, a sodiumtransporter in renal distal convoluted tubule and thus regulates blood pressure. This study was supported by the NIH grant: HL023081, DK039308, HL068686, HL074940, and HL092196