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DOPAMINE MODULATES FLOW‐DEPENDENT TRANSPORT BY NHE3, BUT NOT H + ‐ATPASE, IN MOUSE PROXIMAL TUBULES
Author(s) -
Du zhaopeng,
Gotoh Nanami,
Weinbaum Sheldon,
Weinstein Alan M,
Wang Tong
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.1041.18
Subject(s) - reabsorption , chemistry , endocrinology , medicine , dopamine , stimulation , perfusion , sulpiride , atpase , fenoldopam , kidney , biophysics , enzyme , biology , biochemistry , dopamine receptor , dopaminergic
Mechanism of flow dependence of NaCl and HCO 3 − absorption were studied in microperfused mouse kidney proximal tubules in vitro under the conditions of low (5nl/min) and high (20 nl/min) luminal perfusion rates. Similar to our previous report, the transition from low to high flow increased reabsorption of fluid (J v ) and Na + (J Na ) by 53%, and of HCO 3 − (J HCO3 ) by 100%. Flow did not affect Cl − transport, as J Cl was 47.8 and 40.5 pmol/min/mm at high and low flow rates, respectively. Luminal dopamine (DA; 10μM) did not change J Na and J HCO3 at low flow rate but completely abolished the increments of J Na and partially inhibited (60%) the increment of J HCO3 induced by high flow rate. The remaining flow‐stimulated J HCO3 in the presence of DA was completely abolished by luminal bafilomycin, an inhibitor of H + ‐ATPase. The effect of DA was largely blocked by DA1 inhibitor SCH23390 and completely blocked when both DA1 and DA2 inhibitors, SCH23390 and sulpiride, were added together. The effect of DA was abolished by the protein kinase A inhibitor H89; however, 8‐Br‐cAMP had no effect on flow‐dependent stimulation of proximal tubule transport. 8‐Br‐cAMP had a similar inhibitory effect on J Na and J HCO3 at both low and high flow rates. J Na was reduced by 21% and 24.5 % and J HCO3 by 16% and 16.5% compared with control at low and high perfusion rates, respectively. These results show that flow dependence of NHE3 and H + ‐ATPase is cAMP independent and dopamine interferes with the flow dependence of NHE3 largely by a DA1‐ and PKA‐mediated mechanism but has no impact on H + ‐ATPase, indicating flow dependence of NHE3 and H + ‐ATPase activity may be modulated by different signaling mechanisms.