Stimulation of Na(+)-K(+)-2Cl- cotransport in rat medullary thick ascending limb by dopamine.
Dopamine receptors are present in the medullary thick ascending limb (mTAL) of Henle, but their effect on ion transport in this nephron segment has not been tested. Therefore, we studied the short-term effects of dopamine on Na(+)-K(+)-2Cl- cotransport (assessed by 100 microM bumetanide-sensitive 86Rb uptake) in rat mTAL tubular suspensions. Dopamine (1 microM) stimulated bumetanide-sensitive 86Rb uptake (72.1 +/- 10.6% vs. control, n = 5) by increasing total 86Rb uptake and by decreasing bumetanide-insensitive 86Rb uptake; this effect was concentration dependent. The dopamine-induced stimulation of Na(+)-K(+)-2Cl- cotransport activity was mimicked by calyculin A, a protein phosphatase (PP) inhibitor, and Sp isomer of adenosine 3',5'-cyclic monophosphothioate (Sp-cAMP[S]), a protein kinase A (PKA) agonist, and blocked by Rp isomer of 8-(4-chlorophenylthio)-cAMP[S] (Rp-8-CPT-cAMP[S]), a PKA inhibitor (n = 5). Dopamine did not increase the stimulatory effect of the PP inhibitor. However, the stimulatory effect of the PP inhibitor and PKA agonist was additive and approached the stimulatory effect of dopamine. The stimulatory effects of dopamine, PP inhibitor, and PKA agonist persisted even when intracellular sodium was clamped by 5 microM monensin. When K+ channels were blocked by 1 mM BaCl2, the effects of dopamine and calyculin A on the cotransport were no longer apparent, although the stimulatory effect of the PKA agonist was attenuated. We conclude that dopamine stimulates Na(+)-K(+)-2Cl- cotransport activity. This action is mediated mainly by PKA-dependent phosphorylation/dephosphorylation processes and modulated by dopamine actions on K+ channels.
Aoki
Y
Y
Second Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Albrecht
F E
FE
Bergman
K R
KR
Jose
P A
PA
D000818:Animals; D017609:Barium Compounds / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D002712:Chlorides / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000819:agonists / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007536:Isomerism; D007679:Kidney Medulla; D008138:Loop of Henle / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism*; D008387:Marine Toxins; D010080:Oxazoles / Q000494:pharmacology; D026902:Potassium Channel Blockers; D051381:Rats; D011921:Rats, Inbred WKY; D028021:Sodium-Potassium-Chloride Symporters; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013873:Thionucleotides / Q000494:pharmacology
D017609:Barium Compounds; D002352:Carrier Proteins; D002712:Chlorides; D004791:Enzyme Inhibitors; D008387:Marine Toxins; D010080:Oxazoles; D026902:Potassium Channel Blockers; D028021:Sodium-Potassium-Chloride Symporters; D013873:Thionucleotides; C024986:barium chloride; C016957:adenosine-3',5'-cyclic phosphorothioate; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; C059041:calyculin A; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000254:Sodium-Potassium-Exchanging ATPase; D004298:Dopamine