Role of tyrosine kinase and p44/42 MAPK in D(2)-like receptor-mediated stimulation of Na(+), K(+)-ATPase in kidney.
Our laboratory has shown that dopamine D(2)-like receptor activation causes stimulation of Na(+), K(+)-ATPase (NKA) activity in the proximal tubules of the rat kidney. The present study was designed to investigate the cellular signaling mechanisms mediating this response to D(2)-like receptor activation. We measured the stimulation of NKA activity by bromocriptine (D(2)-like receptor agonist) in the absence and presence of PD-98059 [p44/42 mitogen-activated protein kinase (MAPK) kinase inhibitor] and genistein (tyrosine kinase inhibitor) in renal proximal tubules. Both agents inhibited bromocriptine-mediated stimulation of NKA, suggesting the involvement of p44/42 MAPK and tyrosine kinase in this response. Additionally, we found that bromocriptine increased the phosphorylation of p44/42 MAPK in the proximal tubules, which was blocked by PD-98059 and genistein. These results show that D(2)-like receptor activation causes stimulation of NKA activity by means of a tyrosine kinase-p44/42 MAPK pathway in the proximal tubules of the kidney.
Narkar
Vihang
V
Institute for Cardiovascular Studies, College of Pharmacy, University of Houston, Houston, Texas 77204-5515, USA.
Hussain
Tahir
T
Lokhandwala
Mustafa
M
D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D004294:Domperidone / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000201:enzymology; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013268:Stimulation, Chemical; D014638:Vanadates / Q000494:pharmacology
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D004791:Enzyme Inhibitors; D005419:Flavonoids; D017448:Receptors, Dopamine D2; D001971:Bromocriptine; D014638:Vanadates; D004294:Domperidone; D003994:Bucladesine; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D000254:Sodium-Potassium-Exchanging ATPase; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one