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Published on: September 1, 2015
Prostaglandin E₂ modulates proximal tubule Na+-ATPase activity: cooperative effect between protein kinase A and
J D Líbano-Soares1, S S Landgraf, E Gomes-Quintana
1Instituto de Biofísica Carlos Chagas Filho/UFRJ, CCS-Bloco G, 21949-900 Rio de Janeiro, RJ, Brazil.
Abstract:
Previous data showed that prostaglandin E₂ (PGE₂) mediates the inhibitory effect of bradykinin (BK) on proximal tubule (PT) Na+-ATPase activity. The aim of this work was to investigate the molecular mechanisms involved in the effect of PGE₂ on PT Na+-ATPase. We used isolated basolateral membrane (BLM) from pig PT, which expresses several components of different signaling pathways. The inhibitory effect of PGE₂ on PT Na+-ATPase activity involves G-protein and the activation of protein kinase A (PKA) because: (1) PGE₂ increased [³⁵S]GTPγS binding; (2) GDPβS abolished the inhibitory effect of PGE₂; (3) PGE₂ increased PKA activity; (4) the inhibitory effect of PGE₂ was abolished by PKA inhibitor peptide. We observed that the PKA-mediated inhibitory effect of PGE₂ on PT Na+-ATPase activity requires previous activation of protein kinase C. In addition, we observed that PGE₂ stimulates Ca²+-independent phospholipase A₂ activity representing an important positive feedback to maintain the inhibition of the enzyme. These results open new perspectives to understanding the mechanism involved in the effect of PGE₂ on proximal tubule sodium reabsorption.
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