Activation of D2-like receptors causes recruitment of tyrosine-phosphorylated NKA alpha 1-subunits in kidney.
The present study investigates the cellular mechanisms responsible for dopamine D2-like receptor-mediated stimulation of Na+ - K+-ATPase in the proximal tubules of the kidney. Previously, we showed that D2-like receptor-mediated increase in Na+ - K+-ATPase involves an increase in the maximum rate of Na+ - K+-ATPase activity (V(max)). Therefore, we tested the hypothesis that D2-like receptor-mediated stimulation of Na+ - K+-ATPase requires phosphorylation and recruitment of alpha 1-subunits of the enzyme from cytosol to the membrane. This hypothesis was tested by Western blotting for Na+ - K+-ATPase alpha 1-subunits in proximal tubular membrane. Treatment of the proximal tubules with bromocriptine (D2-like receptor agonist) caused an increase in Na+ - K+-ATPase alpha 1-subunit abundance in the membrane preparations. This effect was blocked by genistein (tyrosine kinase inhibitor), suggesting a role for tyrosine phosphorylation. Moreover, bromocriptine caused an increase in tyrosine phosphorylation of membrane-bound Na+ - K+-ATPase alpha 1-subunits. This effect was blocked by bafilomycin A1 (vesicular trafficking inhibitor), which suggested that this increase was due to the recruitment of tyrosine-phosphorylated Na+ - K+-ATPase alpha 1-subunits. In conclusion, we have demonstrated that activation of D2-like receptors increases Na+ - K+-ATPase activity by recruitment of the tyrosine-phosphorylated alpha 1-subunits in the proximal tubules of the kidney.
Narkar
Vihang A
VA
Institute for Cardiovascular Studies, College of Pharmacy, University of Houston, Houston, Texas 77204-5515, USA.
Hussain
Tahir
T
Lokhandwala
Mustafa F
MF
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001971:Bromocriptine / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D018942:Macrolides; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D018942:Macrolides; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D001971:Bromocriptine; D014443:Tyrosine; C040929:bafilomycin A1; D019833:Genistein; D000254:Sodium-Potassium-Exchanging ATPase