Pflügers Archiv

, Volume 429, Issue 6, pp 832–840 | Cite as

Mechanisms of dopamine effects on Na-K-ATPase activity in Madin-Darby canine kidney (MDCK) epithelial cells

  • Mehrak Shahedi
  • Kathleen Laborde
  • Sharareh Azimi
  • Saidia Hamdani
  • Charles Sachs
Original Article Transport Processes, Metabolism and Endocrinology; Kidney, Gastrointestinal Tract, and Exocrine Glands


Dopamine decreases tubular sodium reabsorption, attributed in part to Na-K-ATPase inhibition in the proximal convoluted tubule (PCT). Because the final regulation of sodium excretion occurs in the collecting duct, where specific dopamine DA1 binding sites have been demonstrated, we examined the effects of dopamine, as well as of DA1 and DA2 receptor agonists on Na-K-ATPase activity and on the number of units in Madin-Darby canine kidney (MDCK) cells, which retain differentiated properties of the renal cortical collecting tubule epithelium. Dopamine (10−5 M) inhibited pump activity (by 50%) and reduced the number of units. This effect was reproduced by the DA1 agonist SKF 38393, which inhibited pump activity in a dose- and time-dependent manner (maximum, 10−5 M). The DA2 agonist quinpirole hydrochloride was without effect, either alone or in combination with SKF 38393. Inhibition of pump activity by dopamine was totally abolished by H7 (100 μM), an inhibitor of protein kinase (PK), but partially by 2′, 5′-dideoxyadenosine (DDA) and H4, respective inhibitors of cAMP production and PKA, which suggests that the dopamine effect on Na-K-ATPase activity may be linked to activation of both PKC and PKA. In these cells, amiloride addition during preincubation did not alter the effect of dopamine on Na-K-ATPase activity; in contrast, furosemide increased further the inhibitory effect of dopamine on the enzyme activity. Monensin addition (10−3 M) reversed the inhibitory effect of dopamine after a 30-min preincubation. These results indicate that dopamine inhibits Na-K-ATPase activity in MDCK cells and that this inhibition is mediated by activation of the DA1 receptor, they also suggest that PKC and PKA activation inhibits apical sodium entry.

Key words

Dopamine Na-K-ATPase MDCK 


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Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • Mehrak Shahedi
    • 1
  • Kathleen Laborde
    • 1
  • Sharareh Azimi
    • 1
  • Saidia Hamdani
    • 1
  • Charles Sachs
    • 1
  1. 1.Département de PhysiologieFaculté de Médecine Necker Enfants MaladesParisFrance

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