Premium
ROLE OF DOPAMINE IN MODULATING FLOW‐DEPENDENT SODIUM AND BICARBONATE TRANSPORT IN MOUSE PROXIMAL TUBULE
Author(s) -
Du Zhaopeng,
Yan QingShang,
Weinbaum Sheldon,
Weinstein Alan M,
Wang Tong
Publication year - 2010
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.24.1_supplement.1024.2
Subject(s) - chemistry , reabsorption , dopamine , endocrinology , medicine , sulpiride , tubule , stimulation , fenoldopam , renal sodium reabsorption , dopamine receptor , biophysics , kidney , biology , dopaminergic
We have previously demonstrated that increases in luminal flow rate produce proportional increases in Na + reabsorption by mouse proximal tubules. Since dopamine inhibits sodium reabsorption by stimulating NHE3 endocytosis and antagonizes the stimulation of proximal tubule transport by norepinephrine, we investigated whether increase of NHE3 endocytosis by dopamine will block flow‐stimulation of proximal tubule transport. Mouse proximal tubules were microperfused in vitro at perfusion rates of 5 and 20nl/min, and the net reabsorption of fluid (J v ) and HCO 3 − (J HCO3 ) were measured. The effect of dopamine and dopamine receptor inhibitors SCH23390 (DA1), sulpiride (DA2), 8‐Bromo‐cAMP and a cAMP‐dependent protein kinase inhibitor H89 on flow‐stimulated proximal tubule transport was examined. Increase in perfusion rate from 5 to 20nl/min significantly increased J v from 0.88 to 1.5 nl/min/mm and J HCO3 from 61.72 to 128.53 pmole/min/mm. Luminal dopamine did not change Jv and J HCO3 at low flow rate but abolished the increments of J v and J HCO3 induced by high flow rate. SCH23390 completely blocked, but sulpiride partially blocked the effect of dopamine. 8‐Bromo‐cAMP reduced J v and J HCO3 at both flow rates and the effect of dopamine was blocked by H89. These results indicate that dopamine activates its receptor and inhibits flow‐stimulated proximal tubule transport by a PKA‐mediated mechanism. Recruitment of NHE3 to the apical membrane is critical for flow‐stimulated Na + and HCO 3 − absorption in the kidney proximal tubule.