Bradykinin B1 receptor stimulates the proximal tubule Na+-ATPase activity through protein kinase C pathway

Abstract Recently, our group described a B 1 -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.