The stimulatory effect of angiotensin II on Na(+)-ATPase activity involves sequential activation of phospholipases and sustained PKC activity.
Angiotensin II (Ang II) stimulates the proximal tubule Na(+)-ATPase through the AT(1) receptor/phosphoinositide phospholipase Cbeta (PI-PLCbeta)/protein kinase C (PKC) pathway. However, this pathway alone does not explain the sustained effect of Ang II on Na(+)-ATPase activity for 30 min. The aim of the present work was to elucidate the molecular mechanisms involved in the sustained effect of Ang II on Na(+)-ATPase activity. Ang II induced fast and correlated activation of Na(+)-ATPase and PKC activities with the maximal effect (115%) observed at 1 min and sustained for 30 min, indicating a pivotal role of PKC in the modulation of Na(+)-ATPase by Ang II. We observed that the sustained activation of PKC by Ang II depended on the sequential activation of phospholipase D and Ca(2+)-insensitive phospholipase A(2), forming phosphatidic acid and lysophosphatidic acid, respectively. The results indicate that PKC could be the final target and an integrator molecule of different signaling pathways triggered by Ang II, which could explain the sustained activation of Na(+)-ATPase by Ang II.
De Souza
Aloa Machado
AM
Instituto Federal de Educação Ciência e Tecnologia do Rio de Janeiro, Lúcio Tavares 1045, 26350-060 Centro, Nilópolis, Rio de Janeiro, Brazil.
de Carvalho
Thaís Louise Gurjão
TL
Lara
Lucienne da Silva
Lda S
Gomes-Quintana
Elaine
E
Lopes
Anibal Gil
AG
Caruso-Neves
Celso
C
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D008246:Lysophospholipids / Q000378:metabolism; D008566:Membranes / Q000187:drug effects; D010712:Phosphatidic Acids / Q000494:pharmacology; D010739:Phospholipase D / Q000378:metabolism*; D054467:Phospholipases A2 / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D034421:Sus scrofa; D013997:Time Factors
D008246:Lysophospholipids; D010712:Phosphatidic Acids; D000804:Angiotensin II; D011493:Protein Kinase C; D054467:Phospholipases A2; D010739:Phospholipase D; D000254:Sodium-Potassium-Exchanging ATPase; C032881:lysophosphatidic acid