title: Prostaglandin E₂ modulates proximal tubule Na+-ATPase activity: cooperative effect between protein kinase A and protein kinase C.
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.
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho/UFRJ, CCS-Bloco G, 21949-900 Rio de Janeiro, RJ, Brazil.
authors.forename: J D
authors.initials: JD
authors.lastname: Líbano-Soares
authors.forename: S S
authors.initials: SS
authors.lastname: Landgraf
authors.forename: E
authors.initials: E
authors.lastname: Gomes-Quintana
authors.forename: A G
authors.initials: AG
authors.lastname: Lopes
authors.forename: C
authors.initials: C
authors.lastname: Caruso-Neves
mesh_terms: D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D027682:Cation Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D025461:Feedback, Physiological / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D066298:In Vitro Techniques; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D054512:Phospholipases A2, Calcium-Independent / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D055503:Protein Multimerization / Q000187:drug effects
chemical_list: D027682:Cation Transport Proteins; D004791:Enzyme Inhibitors; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D054512:Phospholipases A2, Calcium-Independent; D000251:Adenosine Triphosphatases; D019204:GTP-Binding Proteins; C021838:sodium-translocating ATPase; D015232:Dinoprostone; D001920:Bradykinin