Bradykinin B1 receptor stimulates the proximal tubule Na(+)-ATPase activity through protein kinase C pathway.
Recently, our group described a B1-mediated stimulatory effect of des-Arg(9)-bradykinin (DABK) on the Na(+)-ATPase activity of proximal tubule basolateral membranes (BLM) [Biochim. Biophys. Acta 1431 (1999) 483.]. Data in the present report suggest the participation of a phosphatidylinositol-specific PLC (PI-PLC)/protein kinase C (PKC) pathway as the molecular mechanism of DABK-mediated stimulation of the Na(+)-ATPase activity since (i) 10(-8) M DABK activates PI-PLC activity; (ii) 10(-9) M U73122, a PI-PLC inhibitor, abolishes the effect of 10(-8) M DABK on the Na(+)-ATPase activity; (iii) 10(-8) M DABK increases phosphoprotein formation by 34%. This effect is completely reversed by 10(-7) M calphostin C, an inhibitor of PKC; (iv) 20 ng/ml TPA, an activator of PKC, and 10(-8) M DABK stimulate the Na(+)-ATPase activity in a similar and nonadditive manner. Furthermore, the effect of 10(-8) M DABK is completely reversed by calphostin C; (v) 10(-8) M DABK increases phosphoserine residue levels by 54%. This effect is completely reversed by 10(-7) M calphostin C.
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Instituto de Biofísica Carlos Chagas Filho-UFRJ, Universidade Federal do Rio de Janeiro, CCS-Bloco G, 21949-900-Rio de Janeiro, RJ, Brazil.
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D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D027682:Cation Transport Proteins / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000201:enzymology*; D009281:Naphthalenes / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D043783:Receptor, Bradykinin B1 / Q000502:physiology*; D013552:Swine
D027682:Cation Transport Proteins; D004791:Enzyme Inhibitors; D009281:Naphthalenes; D010716:Phosphatidylinositols; D043783:Receptor, Bradykinin B1; D010768:Phosphoserine; C051090:bradykinin, Leu(8)-des-Arg(9)-; D011493:Protein Kinase C; D000251:Adenosine Triphosphatases; C021838:sodium-translocating ATPase; C058819:calphostin C; D001920:Bradykinin